A bone morphogenetic protein that plays an essential role in the regulation of ovarian folliculogenesis.
A growth differentiation factor that is secreted in response to cell stress and in response to MACROPHAGE ACTIVATION. In addition growth differentiation factor 15 demonstrates a diverse array of biological properties including the induction of cartilage formation, the inhibition of hematopoietic progenitor proliferation, and the induction of neuronal migration.
A growth differentiation factor that plays a role in early CHONDROGENESIS and joint formation.
A family of BONE MORPHOGENETIC PROTEIN-related proteins that are primarily involved in regulation of CELL DIFFERENTIATION.
A growth differentiation factor that plays a role in the neural differentiation, specifically in the retinal development of the EYE.
A growth differentiation factor that plays a role in the genesis of left-right asymmetry during vertebrate development. Evidence for this role is seen in MICE where loss of growth differentiation factor 1 function results in right-left isomerism of visceral organs. In HUMANS heterozygous loss of growth differentiation factor 1 function has been associated with CONGENITAL HEART DEFECTS and TRANSPOSITION OF GREAT VESSELS.
A protein that plays a role in GRANULOSA CELLS where it regulates folliculogenesis. Mutations in the gene for bone morphogenetic protein 15 are linked to reproductive abnormalities such as PREMATURE OVARIAN FAILURE.
A growth differentiation factor that may play a role in maintaining the undifferentiated state of PLURIPOTENT STEM CELLS by inhibiting the actions of BONE MORPHOGENETIC PROTEINS. Differentiation factor 3 is also considered a nodal signaling ligand that influences the genesis of left-right asymmetry.
A growth differentiation factor that is closely-related in structure to BONE MORPHOGENETIC PROTEIN 3. Growth differentiation factor 10 is found at high levels in BONE, however it plays an additional roles in regulating EMBRYONIC DEVELOPMENT.
Bone-growth regulatory factors that are members of the transforming growth factor-beta superfamily of proteins. They are synthesized as large precursor molecules which are cleaved by proteolytic enzymes. The active form can consist of a dimer of two identical proteins or a heterodimer of two related bone morphogenetic proteins.
Regulatory proteins and peptides that are signaling molecules involved in the process of PARACRINE COMMUNICATION. They are generally considered factors that are expressed by one cell and are responded to by receptors on another nearby cell. They are distinguished from HORMONES in that their actions are local rather than distal.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
The granulosa cells of the cumulus oophorus which surround the OVUM in the GRAAFIAN FOLLICLE. At OVULATION they are extruded with OVUM.
Supporting cells for the developing female gamete in the OVARY. They are derived from the coelomic epithelial cells of the gonadal ridge. Granulosa cells form a single layer around the OOCYTE in the primordial ovarian follicle and advance to form a multilayered cumulus oophorus surrounding the OVUM in the Graafian follicle. The major functions of granulosa cells include the production of steroids and LH receptors (RECEPTORS, LH).
A growth differentiation factor that is a potent inhibitor of SKELETAL MUSCLE growth. It may play a role in the regulation of MYOGENESIS and in muscle maintenance during adulthood.
An OOCYTE-containing structure in the cortex of the OVARY. The oocyte is enclosed by a layer of GRANULOSA CELLS providing a nourishing microenvironment (FOLLICULAR FLUID). The number and size of follicles vary depending on the age and reproductive state of the female. The growing follicles are divided into five stages: primary, secondary, tertiary, Graafian, and atretic. Follicular growth and steroidogenesis depend on the presence of GONADOTROPINS.
An intracellular signaling adaptor protein that plays a role in TOLL-LIKE RECEPTOR and INTERLEUKIN 1 RECEPTORS signal transduction. It forms a signaling complex with the activated cell surface receptors and members of the IRAK KINASES.
The reproductive organ (GONADS) in female animals. In vertebrates, the ovary contains two functional parts: the OVARIAN FOLLICLE for the production of female germ cells (OOGENESIS); and the endocrine cells (GRANULOSA CELLS; THECA CELLS; and LUTEAL CELLS) for the production of ESTROGENS and PROGESTERONE.
Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).
A family of proteins that are involved in the translocation of signals from TGF-BETA RECEPTORS; BONE MORPHOGENETIC PROTEIN RECEPTORS; and other surface receptors to the CELL NUCLEUS. They were originally identified as a class of proteins that are related to the mothers against decapentaplegic protein, Drosophila and sma proteins from CAENORHABDITIS ELEGANS.
A broadly distributed protein that binds directly to ACTIVINS. It functions as an activin antagonist, inhibits FOLLICLE STIMULATING HORMONE secretion, regulates CELL DIFFERENTIATION, and plays an important role in embryogenesis. Follistatin is a single glycosylated polypeptide chain of approximately 37-kDa and is not a member of the inhibin family (INHIBINS). Follistatin also binds and neutralizes many members of the TRANSFORMING GROWTH FACTOR BETA family.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.
Signal molecules that are involved in the control of cell growth and differentiation.
A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Forms of hepcidin, a cationic amphipathic peptide synthesized in the liver as a prepropeptide which is first processed into prohepcidin and then into the biologically active hepcidin forms, including in human the 20-, 22-, and 25-amino acid residue peptide forms. Hepcidin acts as a homeostatic regulators of iron metabolism and also possesses antimicrobial activity.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
A family of peptides originally found as factors that stimulate the phosphorylation of the erbB-2 receptor (RECEPTORS, ERBB-2). Multiple variant forms of NEUREGULINS occur due to alternative splicing of their mRNAs. The NEUREGULINS include products from the three known genes (NGR1; NGR2 and NGR3).
The discharge of an OVUM from a rupturing follicle in the OVARY.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
A growth differentiation factor that plays a regulatory role as a paracrine factor for a diverse array of cell types during EMBRYONIC DEVELOPMENT and in the adult tissues. Growth differentiation factor 2 is also a potent regulator of CHONDROGENESIS and was previously referred to as bone morphogenetic protein 9.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
Inbred C57BL mice are a strain of laboratory mice that have been produced by many generations of brother-sister matings, resulting in a high degree of genetic uniformity and homozygosity, making them widely used for biomedical research, including studies on genetics, immunology, cancer, and neuroscience.
A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS.
Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.
Proteins prepared by recombinant DNA technology.
Transport proteins that carry specific substances in the blood or across cell membranes.
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Locomotor behavior not involving a steering reaction, but in which there may be a turning random in direction. It includes orthokinesis, the rate of movement and klinokinesis, the amount of turning, which are related to the intensity of stimulation.
A subtype of bone morphogenetic protein receptors with high affinity for BONE MORPHOGENETIC PROTEINS. They can interact with and undergo PHOSPHORYLATION by BONE MORPHOGENETIC PROTEIN RECEPTORS, TYPE II. They signal primarily through RECEPTOR-REGULATED SMAD PROTEINS.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
Antigens expressed primarily on the membranes of living cells during sequential stages of maturation and differentiation. As immunologic markers they have high organ and tissue specificity and are useful as probes in studies of normal cell development as well as neoplastic transformation.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Established cell cultures that have the potential to propagate indefinitely.
Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
A pattern recognition receptor that interacts with LYMPHOCYTE ANTIGEN 96 and LIPOPOLYSACCHARIDES. It mediates cellular responses to GRAM-NEGATIVE BACTERIA.
Cellular signaling in which a factor secreted by a cell affects other cells in the local environment. This term is often used to denote the action of INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS on surrounding cells.
A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Follicle-stimulating hormone stimulates GAMETOGENESIS and the supporting cells such as the ovarian GRANULOSA CELLS, the testicular SERTOLI CELLS, and LEYDIG CELLS. FSH consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity.
The period of the MENSTRUAL CYCLE representing follicular growth, increase in ovarian estrogen (ESTROGENS) production, and epithelial proliferation of the ENDOMETRIUM. Follicular phase begins with the onset of MENSTRUATION and ends with OVULATION.
Activins are produced in the pituitary, gonads, and other tissues. By acting locally, they stimulate pituitary FSH secretion and have diverse effects on cell differentiation and embryonic development. Activins are glycoproteins that are hetero- or homodimers of INHIBIN-BETA SUBUNITS.
A receptor-regulated smad protein that undergoes PHOSPHORYLATION by ACTIVIN RECEPTORS, TYPE I. Activated Smad3 can bind directly to DNA, and it regulates TRANSFORMING GROWTH FACTOR BETA and ACTIVIN signaling.
Elements of limited time intervals, contributing to particular results or situations.
Cell-surface proteins that bind transforming growth factor beta and trigger changes influencing the behavior of cells. Two types of transforming growth factor receptors have been recognized. They differ in affinity for different members of the transforming growth factor beta family and in cellular mechanisms of action.
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
A technique for maintaining or growing TISSUE in vitro, usually by DIFFUSION, perifusion, or PERFUSION. The tissue is cultured directly after removal from the host without being dispersed for cell culture.
An important regulator of GENE EXPRESSION during growth and development, and in NEOPLASMS. Tretinoin, also known as retinoic acid and derived from maternal VITAMIN A, is essential for normal GROWTH; and EMBRYONIC DEVELOPMENT. An excess of tretinoin can be teratogenic. It is used in the treatment of PSORIASIS; ACNE VULGARIS; and several other SKIN DISEASES. It has also been approved for use in promyelocytic leukemia (LEUKEMIA, PROMYELOCYTIC, ACUTE).
The developmental history of specific differentiated cell types as traced back to the original STEM CELLS in the embryo.
A family of pattern recognition receptors characterized by an extracellular leucine-rich domain and a cytoplasmic domain that share homology with the INTERLEUKIN 1 RECEPTOR and the DROSOPHILA toll protein. Following pathogen recognition, toll-like receptors recruit and activate a variety of SIGNAL TRANSDUCING ADAPTOR PROTEINS.
A pattern recognition receptor that forms heterodimers with other TOLL-LIKE RECEPTORS. It interacts with multiple ligands including PEPTIDOGLYCAN, bacterial LIPOPROTEINS, lipoarabinomannan, and a variety of PORINS.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
The process in developing sex- or gender-specific tissue, organ, or function after SEX DETERMINATION PROCESSES have set the sex of the GONADS. Major areas of sex differentiation occur in the reproductive tract (GENITALIA) and the brain.
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
A transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B and OSTEOPROTEGERIN. It plays an important role in regulating OSTEOCLAST differentiation and activation.
Glycoproteins found on the membrane or surface of cells.
Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).
Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere.
Cells derived from the BLASTOCYST INNER CELL MASS which forms before implantation in the uterine wall. They retain the ability to divide, proliferate and provide progenitor cells that can differentiate into specialized cells.
The major progestational steroid that is secreted primarily by the CORPUS LUTEUM and the PLACENTA. Progesterone acts on the UTERUS, the MAMMARY GLANDS and the BRAIN. It is required in EMBRYO IMPLANTATION; PREGNANCY maintenance, and the development of mammary tissue for MILK production. Progesterone, converted from PREGNENOLONE, also serves as an intermediate in the biosynthesis of GONADAL STEROID HORMONES and adrenal CORTICOSTEROIDS.
A potent osteoinductive protein that plays a critical role in the differentiation of osteoprogenitor cells into OSTEOBLASTS.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.

Mechanisms of GDF-5 action during skeletal development. (1/133)

Mutations in GDF-5, a member of the TGF-beta superfamily, result in the autosomal recessive syndromes brachypod (bp) in mice and Hunter-Thompson and Grebe-type chondrodysplasias in humans. These syndromes are all characterised by the shortening of the appendicular skeleton and loss or abnormal development of some joints. To investigate how GDF-5 controls skeletogenesis, we overexpressed GDF-5 during chick limb development using the retrovirus, RCASBP. This resulted in up to a 37.5% increase in length of the skeletal elements, which was predominantly due to an increase in the number of chondrocytes. By injecting virus at different stages of development, we show that GDF-5 can increase both the size of the early cartilage condensation and the later developing skeletal element. Using in vitro micromass cultures as a model system to study the early steps of chondrogenesis, we show that GDF-5 increases chondrogenesis in a dose-dependent manner. We did not detect changes in proliferation. However, cell suspension cultures showed that GDF-5 might act at these stages by increasing cell adhesion, a critical determinant of early chondrogenesis. In contrast, pulse labelling experiments of GDF-5-infected limbs showed that at later stages of skeletal development GDF-5 can increase proliferation of chondrocytes. Thus, here we show two mechanisms of how GDF-5 may control different stages of skeletogenesis. Finally, our data show that levels of GDF-5 expression/activity are important in controlling the size of skeletal elements and provides a possible explanation for the variation in the severity of skeletal defects resulting from mutations in GDF-5.  (+info)

Isolation of zebrafish gdf7 and comparative genetic mapping of genes belonging to the growth/differentiation factor 5, 6, 7 subgroup of the TGF-beta superfamily. (2/133)

The Growth/differentiation factor (Gdf) 5, 6, 7 genes form a closely related subgroup belonging to the TGF-beta superfamily. In zebrafish, there are three genes that belong to the Gdf5, 6, 7 subgroup that have been named radar, dynamo, and contact. The genes radar and dynamo both encode proteins most similar to mouse GDF6. The orthologous identity of these genes on the basis of amino acid similarities has not been clear. We have identified gdf7, a fourth zebrafish gene belonging to the Gdf5, 6, 7 subgroup. To assign correct orthologies and to investigate the evolutionary relationships of the human, mouse, and zebrafish Gdf5, 6, 7 subgroup, we have compared genetic map positions of the zebrafish and mammalian genes. We have mapped zebrafish gdf7 to linkage group (LG) 17, contact to LG9, GDF6 to human chromosome (Hsa) 8 and GDF7 to Hsa2p. The radar and dynamo genes have been localized previously to LG16 and LG19, respectively. A comparison of syntenies shared among human, mouse, and zebrafish genomes indicates that gdf7 is the ortholog of mammalian GDF7/Gdf7. LG16 shares syntenic relationships with mouse chromosome (Mmu) 4, including Gdf6. Portions of LG16 and LG19 appear to be duplicate chromosomes, thus suggesting that radar and dynamo are both orthologs of Gdf6. Finally, the mapping data is consistent with contact being the zebrafish ortholog of mammalian GDF5/Gdf5.  (+info)

GDF5 coordinates bone and joint formation during digit development. (3/133)

A functional skeletal system requires the coordinated development of many different tissue types, including cartilage, bones, joints, and tendons. Members of the Bone morphogenetic protein (BMP) family of secreted signaling molecules have been implicated as endogenous regulators of skeletal development. This is based on their expression during bone and joint formation, their ability to induce ectopic bone and cartilage, and the skeletal abnormalities present in animals with mutations in BMP family members. One member of this family, Growth/differentiation factor 5 (GDF5), is encoded by the mouse brachypodism locus. Mice with mutations in this gene show reductions in the length of bones in the limbs, altered formation of bones and joints in the sternum, and a reduction in the number of bones in the digits. The expression pattern of Gdf5 during normal development and the phenotypes seen in mice with single or double mutations in Gdf5 and Bmp5 suggested that Gdf5 has multiple functions in skeletogenesis, including roles in joint and cartilage development. To further understand the function of GDF5 in skeletal development, we assayed the response of developing chick and mouse limbs to recombinant GDF5 protein. The results from these assays, coupled with an analysis of the development of brachypodism digits, indicate that GDF5 is necessary and sufficient for both cartilage development and the restriction of joint formation to the appropriate location. Thus, GDF5 function in the digits demonstrates a link between cartilage development and joint development and is an important determinant of the pattern of bones and articulations in the digits.  (+info)

Combinatorial signaling through BMP receptor IB and GDF5: shaping of the distal mouse limb and the genetics of distal limb diversity. (4/133)

In this study, we use a mouse insertional mutant to delineate gene activities that shape the distal limb skeleton. A recessive mutation that results in brachydactyly was found in a lineage of transgenic mice. Sequences flanking the transgene insertion site were cloned, mapped to chromosome 3, and used to identify the brachydactyly gene as the type IB bone morphogenetic protein receptor, BmprIB (ALK6). Expression analyses in wild-type mice revealed two major classes of BmprIB transcripts. Rather than representing unique coding RNAs generated by alternative splicing of a single pro-mRNA transcribed from one promoter, the distinct isoforms reflect evolution of two BmprIB promoters: one located distally, driving expression in the developing limb skeleton, and one situated proximally, initiating transcription in neural epithelium. The distal promoter is deleted in the insertional mutant, resulting in a regulatory allele (BmprIB(Tg)) lacking cis-sequences necessary for limb BmprIB expression. Mutants fail to generate digit cartilage, indicating that BMPRIB is the physiologic transducer for the formation of digit cartilage from the skeletal blastema. Expansion of BmprIB expression into the limb through acquisition of these distal cis-regulatory sequences appears, therefore, to be an important genetic component driving morphological diversity in distal extremities. GDF5 is a BMP-related signal, which is also required for proper digit formation. Analyses incorporating both Gdf5 and BmprIB(Tg) alleles revealed that BMPRIB regulates chondrogenesis and segmentation through both GDF5-dependent and -independent processes, and that, reciprocally, GDF5 acts through both IB and other type I receptors. Together, these findings provide in vivo support for the concept of combinatorial BMP signaling, in which distinct outcomes result both from a single receptor being triggered by different ligands and from a single ligand binding to different receptors.  (+info)

Mutation and analysis of Dan, the founding member of the Dan family of transforming growth factor beta antagonists. (5/133)

The Dan family of transforming growth factor beta antagonists is a large, evolutionarily conserved family of proteins. Little is known about either the specificity of these antagonists or the biological roles of these proteins. We have characterized Dan, the founding member of this family, with regard to both its biochemical specificity and its biological roles. Although DAN is not an efficient antagonist of BMP-2/4 class signals, we found that DAN was able to interact with GDF-5 in a frog embryo assay, suggesting that DAN may regulate signaling by the GDF-5/6/7 class of BMPs in vivo. Intriguingly, in developing neurons, Dan mRNA was localized to axons, suggesting a potential role for the DAN protein in axonal outgrowth or guidance. Mice lacking Dan activity were generated by gene targeting and displayed subtle, background-dependent defects.  (+info)

Skeletal malformations caused by overexpression of Cbfa1 or its dominant negative form in chondrocytes. (6/133)

During skeletogenesis, cartilage develops to either permanent cartilage that persists through life or transient cartilage that is eventually replaced by bone. However, the mechanism by which cartilage phenotype is specified remains unclarified. Core binding factor alpha1 (Cbfa1) is an essential transcription factor for osteoblast differentiation and bone formation and has the ability to stimulate chondrocyte maturation in vitro. To understand the roles of Cbfa1 in chondrocytes during skeletal development, we generated transgenic mice that overexpress Cbfa1 or a dominant negative (DN)-Cbfa1 in chondrocytes under the control of a type II collagen promoter/enhancer. Both types of transgenic mice displayed dwarfism and skeletal malformations, which, however, resulted from opposite cellular phenotypes. Cbfa1 overexpression caused acceleration of endochondral ossification due to precocious chondrocyte maturation, whereas overexpression of DN-Cbfa1 suppressed maturation and delayed endochondral ossification. In addition, Cbfa1 transgenic mice failed to form most of their joints and permanent cartilage entered the endochondral pathway, whereas most chondrocytes in DN-Cbfa1 transgenic mice retained a marker for permanent cartilage. These data show that temporally and spatially regulated expression of Cbfa1 in chondrocytes is required for skeletogenesis, including formation of joints, permanent cartilages, and endochondral bones.  (+info)

Mutation in bone morphogenetic protein receptor-IB is associated with increased ovulation rate in Booroola Merino ewes. (7/133)

Ewes from the Booroola strain of Australian Merino sheep are characterized by high ovulation rate and litter size. This phenotype is due to the action of the FecB(B) allele of a major gene named FecB, as determined by statistical analysis of phenotypic data. By genetic analysis of 31 informative half-sib families from heterozygous sires, we showed that the FecB locus is situated in the region of ovine chromosome 6 corresponding to the human chromosome 4q22-23 that contains the bone morphogenetic protein receptor IB (BMPR-IB) gene encoding a member of the transforming growth factor-beta (TGF-beta) receptor family. A nonconservative substitution (Q249R) in the BMPR-IB coding sequence was found to be associated fully with the hyperprolificacy phenotype of Booroola ewes. In vitro, ovarian granulosa cells from FecB(B)/FecB(B) ewes were less responsive than granulosa cells from FecB(+)/FecB(+) ewes to the inhibitory effect on steroidogenesis of GDF-5 and BMP-4, natural ligands of BMPR-IB. It is suggested that in FecB(B)/FecB(B) ewes, BMPR-IB would be inactivated partially, leading to an advanced differentiation of granulosa cells and an advanced maturation of ovulatory follicles.  (+info)

Spinal fusion with recombinant human growth and differentiation factor-5 combined with a mineralized collagen matrix. (8/133)

The availability of recombinant osteoinductive growth factors and new osteoconductive matrices offers an alternative to the use of autogenous bone (autograft) for grafting indications. This study evaluates the bone-forming activity of a mineralized collagen matrix combined with recombinant human growth and differentiation factor-5 in a rabbit posterolateral spinal fusion model. The activity of three distinct matrix-growth factor formulations is assessed by radiographic, histologic, and mechanical strength methods. Results show that the radiographic density, histologic quality, and mechanical strength of fusion at 12 weeks post-treatment rank consistently within the treatment groups. Optimal formulations are shown to perform similar to autograft in both the rate and strength of fusion. Fusion rates as high as 80% are observed within specific matrix/growth factor formulations. The average biomechanical strength of treated motion segments in the most efficacious formulation is 82% higher than that obtained with autograft, although this difference is not statistically significant. The fusion mass formed in response to matrix/growth factor formulations is composed of normal trabecular bone with a thin outer cortical plate and modest hematopoietic bone marrow. These results demonstrate that the combination of a mineralized collagen matrix with recombinant human growth and differentiation factor-5 maximizes the inherent conductive and inductive properties of each component, respectively, to provide an effective alternative to autograft for bone grafting procedures.  (+info)

Growth Differentiation Factor 9 (GDF9) is a member of the transforming growth factor-beta (TGF-β) superfamily, which plays crucial roles in various biological processes such as cell growth, differentiation, and apoptosis. Specifically, GDF9 is primarily expressed in oocytes and has essential functions during follicular development and ovulation in the ovary. It regulates granulosa cell proliferation, differentiation, and steroidogenesis, contributing to the maintenance of follicular integrity and promoting follicle growth. Additionally, GDF9 is involved in embryonic development and has been implicated in several reproductive disorders when its expression or function is disrupted.

Growth Differentiation Factor 15 (GDF15) is a member of the transforming growth factor-β (TGF-β) superfamily of cytokines, which are signaling proteins involved in various biological processes such as cell growth, differentiation, and apoptosis. GDF15 was originally identified as a protein induced during the development of the mouse placenta, but it is now known to be widely expressed in various tissues in response to stress, injury, or disease.

GDF15 has been shown to have both pro- and anti-inflammatory effects, depending on the context. It can inhibit the production of pro-inflammatory cytokines and promote the differentiation of regulatory T cells, which help to dampen immune responses. On the other hand, GDF15 has also been shown to induce the expression of pro-inflammatory genes in certain cell types, suggesting that its effects may be context-dependent.

In terms of its role in growth and differentiation, GDF15 has been implicated in a variety of processes, including the regulation of energy metabolism, appetite control, and tissue repair. For example, GDF15 has been shown to inhibit food intake and promote weight loss in both mice and humans, suggesting that it may play a role in the regulation of body weight. Additionally, GDF15 has been implicated in the development of certain diseases, such as cancer, heart disease, and neurological disorders, although its precise role in these conditions is not yet fully understood.

Overall, GDF15 is a multifunctional cytokine that plays important roles in various biological processes, including inflammation, growth, differentiation, and metabolism. Its precise functions and mechanisms of action are still being elucidated, but it is clear that GDF15 has significant potential as a therapeutic target for a variety of diseases.

Growth Differentiation Factor 5 (GDF5) is a member of the transforming growth factor-beta (TGF-β) superfamily of proteins, which are involved in various developmental processes such as cell growth, differentiation, and migration. GDF5 plays crucial roles in skeletal development, joint formation, and cartilage maintenance. It is a secreted signaling molecule that binds to specific receptors on the cell surface, activating intracellular signaling pathways that regulate gene expression and ultimately influence cell behavior.

GDF5 has been associated with several genetic disorders affecting the musculoskeletal system, such as brachydactyly type C (shortened fingers or toes), Grebe's recessive chondrodysplasia (disproportionate short stature and joint deformities), and Hunter-Thompson syndrome (a rare skeletal disorder characterized by abnormal bone growth, joint laxity, and other features). Additionally, GDF5 has been implicated in osteoarthritis, a degenerative joint disease, due to its role in maintaining cartilage homeostasis.

Growth differentiation factors (GDFs) are a subfamily of the transforming growth factor-beta (TGF-β) superfamily of cytokines. They play crucial roles in various biological processes, including cell growth, differentiation, and apoptosis. Specifically, GDFs are involved in the development and maintenance of the skeletal, reproductive, and nervous systems. Some members of this family include GDF5, GDF6, and GDF7, which are essential for normal joint formation and cartilage development; GDF8 (also known as myostatin) is a negative regulator of muscle growth; and GDF11 has been implicated in the regulation of neurogenesis and age-related changes.

Growth Differentiation Factor 6 (GDF6) is a member of the transforming growth factor-beta (TGF-β) superfamily, which plays crucial roles in various biological processes such as cell growth, differentiation, and development. Specifically, GDF6 is involved in the regulation of skeletal development, joint formation, and limb morphogenesis. It has been shown to inhibit chondrogenic differentiation and promote osteogenic differentiation during bone development. Genetic variations in the GDF6 gene have been associated with certain musculoskeletal disorders, such as osteoarthritis and joint laxity.

Growth Differentiation Factor 1 (GDF1), also known as Vascular Endothelial Growth Factor E (VEGE), is a protein that belongs to the transforming growth factor-beta (TGF-β) superfamily. It plays crucial roles in embryonic development, including the regulation of cell growth, differentiation, and apoptosis (programmed cell death). GDF1 is essential for proper patterning and morphogenesis during gastrulation and organogenesis. In adults, GDF1 expression is limited to certain tissues, such as the reproductive system, where it continues to regulate cellular processes.

Bone Morphogenetic Protein 15 (BMP-15) is a growth factor belonging to the transforming growth factor-beta (TGF-β) superfamily. It plays crucial roles in the development and function of the reproductive system, particularly in the ovary. BMP-15 is primarily produced by the oocytes (egg cells) and stimulates the growth and differentiation of granulosa cells, which surround and support the oocytes during follicular development.

BMP-15 has been shown to promote follicular development, increase ovulation rate, and improve embryo quality in various animal models. In humans, mutations in the BMP15 gene have been associated with ovarian dysfunction, including premature ovarian failure and primary ovarian insufficiency. However, the role of BMP-15 in human reproductive physiology is not yet fully understood, and further research is needed to clarify its exact functions and potential clinical applications.

Growth Differentiation Factor 3 (GDF3) is a member of the transforming growth factor-beta (TGF-β) superfamily, which are signaling proteins involved in cell growth, differentiation, and apoptosis. GDF3 plays crucial roles during embryonic development, including mesoderm formation, endoderm differentiation, and left-right patterning. It is also expressed in adult tissues, such as the heart, brain, and reproductive organs, although its functions in these contexts are less well understood. GDF3 is secreted as a dimeric protein and signals through a heteromeric complex of type I and type II serine/threonine kinase receptors, leading to the activation of intracellular SMAD proteins and downstream transcriptional responses.

Growth Differentiation Factor 10 (GDF10), also known as Bone Morphogenetic Protein 3b (BMP3b), is a member of the Transforming Growth Factor-β (TGF-β) superfamily. It is a secreted signaling protein that plays crucial roles in various biological processes, including embryonic development, tissue homeostasis, and repair. Specifically, GDF10 has been implicated in regulating skeletal growth, joint formation, and neural crest cell migration during embryogenesis. In addition, it is involved in the regulation of bone mass, as well as the maintenance and differentiation of mesenchymal stem cells. Dysregulation of GDF10 has been associated with several pathological conditions, such as skeletal disorders and tumorigenesis.

Bone Morphogenetic Proteins (BMPs) are a group of growth factors that play crucial roles in the development, growth, and repair of bones and other tissues. They belong to the Transforming Growth Factor-β (TGF-β) superfamily and were first discovered when researchers found that certain proteins extracted from demineralized bone matrix had the ability to induce new bone formation.

BMPs stimulate the differentiation of mesenchymal stem cells into osteoblasts, which are the cells responsible for bone formation. They also promote the recruitment and proliferation of these cells, enhancing the overall process of bone regeneration. In addition to their role in bone biology, BMPs have been implicated in various other biological processes, including embryonic development, wound healing, and the regulation of fat metabolism.

There are several types of BMPs (BMP-2, BMP-4, BMP-7, etc.) that exhibit distinct functions and expression patterns. Due to their ability to stimulate bone formation, recombinant human BMPs have been used in clinical applications, such as spinal fusion surgery and non-healing fracture treatment. However, the use of BMPs in medicine has been associated with certain risks and complications, including uncontrolled bone growth, inflammation, and cancer development, which necessitates further research to optimize their therapeutic potential.

Intercellular signaling peptides and proteins are molecules that mediate communication and interaction between different cells in living organisms. They play crucial roles in various biological processes, including cell growth, differentiation, migration, and apoptosis (programmed cell death). These signals can be released into the extracellular space, where they bind to specific receptors on the target cell's surface, triggering intracellular signaling cascades that ultimately lead to a response.

Peptides are short chains of amino acids, while proteins are larger molecules made up of one or more polypeptide chains. Both can function as intercellular signaling molecules by acting as ligands for cell surface receptors or by being cleaved from larger precursor proteins and released into the extracellular space. Examples of intercellular signaling peptides and proteins include growth factors, cytokines, chemokines, hormones, neurotransmitters, and their respective receptors.

These molecules contribute to maintaining homeostasis within an organism by coordinating cellular activities across tissues and organs. Dysregulation of intercellular signaling pathways has been implicated in various diseases, such as cancer, autoimmune disorders, and neurodegenerative conditions. Therefore, understanding the mechanisms underlying intercellular signaling is essential for developing targeted therapies to treat these disorders.

Cell differentiation is the process by which a less specialized cell, or stem cell, becomes a more specialized cell type with specific functions and structures. This process involves changes in gene expression, which are regulated by various intracellular signaling pathways and transcription factors. Differentiation results in the development of distinct cell types that make up tissues and organs in multicellular organisms. It is a crucial aspect of embryonic development, tissue repair, and maintenance of homeostasis in the body.

Cumulus cells are a type of specialized cell that surround and support the egg (oocyte) in the ovary of female mammals, including humans. These cells are located in the cumulus oophorus, which is a cluster of cells that surrounds and protects the mature egg within the follicle.

Cumulus cells play an important role in the process of fertilization by providing nutrients to the developing egg and helping to regulate its growth and development. They also help to facilitate communication between the egg and the surrounding follicular cells, which is necessary for the release of the mature egg from the ovary during ovulation.

In addition to their role in reproduction, cumulus cells have been studied for their potential use in various medical applications, including as a source of stem cells for therapeutic purposes. However, more research is needed to fully understand the properties and potential uses of these cells.

Granulosa cells are specialized cells that surround and enclose the developing egg cells (oocytes) in the ovaries. They play a crucial role in the growth, development, and maturation of the follicles (the fluid-filled sacs containing the oocytes) by providing essential nutrients and hormones.

Granulosa cells are responsible for producing estrogen, which supports the development of the endometrium during the menstrual cycle in preparation for a potential pregnancy. They also produce inhibin and activin, two hormones that regulate the function of the pituitary gland and its secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

These cells are critical for female reproductive health and fertility. Abnormalities in granulosa cell function can lead to various reproductive disorders, such as polycystic ovary syndrome (PCOS), premature ovarian failure, and infertility.

Myostatin is a protein that is primarily known for its role in regulating muscle growth. It's also called "growth differentiation factor 8" or GDF-8. Produced by muscle cells, myostatin inhibits the process of muscle growth by preventing the transformation of stem cells into muscle fibers and promoting the breakdown of existing muscle proteins.

In essence, myostatin acts as a negative regulator of muscle mass, keeping it in check to prevent excessive growth. Mutations leading to reduced myostatin activity or expression have been associated with increased muscle mass and strength in both animals and humans, making it a potential target for therapeutic interventions in muscle-wasting conditions such as muscular dystrophy and age-related sarcopenia.

An ovarian follicle is a fluid-filled sac in the ovary that contains an immature egg or ovum (oocyte). It's a part of the female reproductive system and plays a crucial role in the process of ovulation.

Ovarian follicles start developing in the ovaries during fetal development, but only a small number of them will mature and release an egg during a woman's reproductive years. The maturation process is stimulated by hormones like follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

There are different types of ovarian follicles, including primordial, primary, secondary, and tertiary or Graafian follicles. The Graafian follicle is the mature follicle that ruptures during ovulation to release the egg into the fallopian tube, where it may be fertilized by sperm.

It's important to note that abnormal growth or development of ovarian follicles can lead to conditions like polycystic ovary syndrome (PCOS) and ovarian cancer.

Myeloid Differentiation Factor 88 (MYD88) is a signaling adaptor protein that plays a crucial role in the innate immune response. It is involved in the signal transduction pathways of several Toll-like receptors (TLRs), which are pattern recognition receptors that recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs).

Upon activation of TLRs, MYD88 is recruited to the receptor complex where it interacts with IL-1 receptor-associated kinase 4 (IRAK4) and activates IRAK1. This leads to the activation of downstream signaling pathways, including the mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB), resulting in the production of proinflammatory cytokines and type I interferons.

MYD88 is widely expressed in various cell types, including hematopoietic cells, endothelial cells, and fibroblasts. Mutations in MYD88 have been associated with several human diseases, such as lymphomas, leukemias, and autoimmune disorders.

An ovary is a part of the female reproductive system in which ova or eggs are produced through the process of oogenesis. They are a pair of solid, almond-shaped structures located one on each side of the uterus within the pelvic cavity. Each ovary measures about 3 to 5 centimeters in length and weighs around 14 grams.

The ovaries have two main functions: endocrine (hormonal) function and reproductive function. They produce and release eggs (ovulation) responsible for potential fertilization and development of an embryo/fetus during pregnancy. Additionally, they are essential in the production of female sex hormones, primarily estrogen and progesterone, which regulate menstrual cycles, sexual development, and reproduction.

During each menstrual cycle, a mature egg is released from one of the ovaries into the fallopian tube, where it may be fertilized by sperm. If not fertilized, the egg, along with the uterine lining, will be shed, leading to menstruation.

An oocyte, also known as an egg cell or female gamete, is a large specialized cell found in the ovary of female organisms. It contains half the number of chromosomes as a normal diploid cell, as it is the product of meiotic division. Oocytes are surrounded by follicle cells and are responsible for the production of female offspring upon fertilization with sperm. The term "oocyte" specifically refers to the immature egg cell before it reaches full maturity and is ready for fertilization, at which point it is referred to as an ovum or egg.

Smad proteins are a family of intracellular signaling molecules that play a crucial role in the transmission of signals from the cell surface to the nucleus in response to transforming growth factor β (TGF-β) superfamily ligands. These ligands include TGF-βs, bone morphogenetic proteins (BMPs), activins, and inhibins.

There are eight mammalian Smad proteins, which are categorized into three classes based on their function: receptor-regulated Smads (R-Smads), common mediator Smads (Co-Smads), and inhibitory Smads (I-Smads). R-Smads include Smad1, Smad2, Smad3, Smad5, and Smad8/9, while Smad4 is the only Co-Smad. The I-Smads consist of Smad6 and Smad7.

Upon TGF-β superfamily ligand binding to their transmembrane serine/threonine kinase receptors, R-Smads are phosphorylated and form complexes with Co-Smad4. These complexes then translocate into the nucleus, where they regulate the transcription of target genes involved in various cellular processes, such as proliferation, differentiation, apoptosis, migration, and extracellular matrix production. I-Smads act as negative regulators of TGF-β signaling by competing with R-Smads for receptor binding or promoting the degradation of receptors and R-Smads.

Dysregulation of Smad protein function has been implicated in various human diseases, including fibrosis, cancer, and developmental disorders.

Follistatin is a glycoprotein that is naturally produced in various tissues, including the ovaries, pituitary gland, and skeletal muscle. It plays an essential role in regulating the activity of members of the transforming growth factor-β (TGF-β) superfamily, particularly the bone morphogenetic proteins (BMPs) and activins.

Follistatin binds to these signaling molecules with high affinity, preventing them from interacting with their receptors and thereby inhibiting their downstream signaling pathways. By doing so, follistatin helps regulate processes such as follicle stimulation in the ovaries, neurogenesis, muscle growth, and inflammation.

Increased levels of follistatin have been associated with muscle hypertrophy, while its deficiency can lead to impaired fertility and developmental abnormalities.

Developmental gene expression regulation refers to the processes that control the activation or repression of specific genes during embryonic and fetal development. These regulatory mechanisms ensure that genes are expressed at the right time, in the right cells, and at appropriate levels to guide proper growth, differentiation, and morphogenesis of an organism.

Developmental gene expression regulation is a complex and dynamic process involving various molecular players, such as transcription factors, chromatin modifiers, non-coding RNAs, and signaling molecules. These regulators can interact with cis-regulatory elements, like enhancers and promoters, to fine-tune the spatiotemporal patterns of gene expression during development.

Dysregulation of developmental gene expression can lead to various congenital disorders and developmental abnormalities. Therefore, understanding the principles and mechanisms governing developmental gene expression regulation is crucial for uncovering the etiology of developmental diseases and devising potential therapeutic strategies.

Growth substances, in the context of medical terminology, typically refer to natural hormones or chemically synthesized agents that play crucial roles in controlling and regulating cell growth, differentiation, and division. They are also known as "growth factors" or "mitogens." These substances include:

1. Proteins: Examples include insulin-like growth factors (IGFs), transforming growth factor-beta (TGF-β), platelet-derived growth factor (PDGF), and fibroblast growth factors (FGFs). They bind to specific receptors on the cell surface, activating intracellular signaling pathways that promote cell proliferation, differentiation, and survival.

2. Steroids: Certain steroid hormones, such as androgens and estrogens, can also act as growth substances by binding to nuclear receptors and influencing gene expression related to cell growth and division.

3. Cytokines: Some cytokines, like interleukins (ILs) and hematopoietic growth factors (HGFs), contribute to the regulation of hematopoiesis, immune responses, and inflammation, thus indirectly affecting cell growth and differentiation.

These growth substances have essential roles in various physiological processes, such as embryonic development, tissue repair, and wound healing. However, abnormal or excessive production or response to these growth substances can lead to pathological conditions, including cancer, benign tumors, and other proliferative disorders.

Transforming Growth Factor-beta (TGF-β) is a type of cytokine, which is a cell signaling protein involved in the regulation of various cellular processes, including cell growth, differentiation, and apoptosis (programmed cell death). TGF-β plays a critical role in embryonic development, tissue homeostasis, and wound healing. It also has been implicated in several pathological conditions such as fibrosis, cancer, and autoimmune diseases.

TGF-β exists in multiple isoforms (TGF-β1, TGF-β2, and TGF-β3) that are produced by many different cell types, including immune cells, epithelial cells, and fibroblasts. The protein is synthesized as a precursor molecule, which is cleaved to release the active TGF-β peptide. Once activated, TGF-β binds to its receptors on the cell surface, leading to the activation of intracellular signaling pathways that regulate gene expression and cell behavior.

In summary, Transforming Growth Factor-beta (TGF-β) is a multifunctional cytokine involved in various cellular processes, including cell growth, differentiation, apoptosis, embryonic development, tissue homeostasis, and wound healing. It has been implicated in several pathological conditions such as fibrosis, cancer, and autoimmune diseases.

Messenger RNA (mRNA) is a type of RNA (ribonucleic acid) that carries genetic information copied from DNA in the form of a series of three-base code "words," each of which specifies a particular amino acid. This information is used by the cell's machinery to construct proteins, a process known as translation. After being transcribed from DNA, mRNA travels out of the nucleus to the ribosomes in the cytoplasm where protein synthesis occurs. Once the protein has been synthesized, the mRNA may be degraded and recycled. Post-transcriptional modifications can also occur to mRNA, such as alternative splicing and addition of a 5' cap and a poly(A) tail, which can affect its stability, localization, and translation efficiency.

Signal transduction is the process by which a cell converts an extracellular signal, such as a hormone or neurotransmitter, into an intracellular response. This involves a series of molecular events that transmit the signal from the cell surface to the interior of the cell, ultimately resulting in changes in gene expression, protein activity, or metabolism.

The process typically begins with the binding of the extracellular signal to a receptor located on the cell membrane. This binding event activates the receptor, which then triggers a cascade of intracellular signaling molecules, such as second messengers, protein kinases, and ion channels. These molecules amplify and propagate the signal, ultimately leading to the activation or inhibition of specific cellular responses.

Signal transduction pathways are highly regulated and can be modulated by various factors, including other signaling molecules, post-translational modifications, and feedback mechanisms. Dysregulation of these pathways has been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.

Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.

It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.

Hepcidin is a peptide hormone primarily produced in the liver that plays a crucial role in regulating iron homeostasis within the body. It acts by inhibiting the absorption of dietary iron in the intestines and the release of iron from storage sites, such as macrophages, into the bloodstream. By reducing the amount of iron available for use, hepcidin helps prevent excessive iron accumulation in tissues, which can be harmful and contribute to the development of various diseases, including iron overload disorders and certain types of anemia. The production of hepcidin is regulated by several factors, including iron levels, inflammation, and erythropoiesis (the production of red blood cells).

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

Neuregulins are a family of growth factors that play important roles in the development and maintenance of the nervous system. They bind to and activate receptors known as ErbB receptors, which are tyrosine kinase receptors. Neuregulins are involved in the regulation of various cellular processes, including proliferation, differentiation, migration, and survival.

There are several different forms of neuregulins, which are produced by alternative splicing of a single gene. These forms include heregulin, glial growth factor, and neu differentiation factor. Neuregulins are produced by various cell types in the nervous system, including neurons and glial cells. They are involved in the development and maintenance of the nervous system, including the formation of synapses, the regulation of myelination, and the survival of neurons.

Dysregulation of neuregulin signaling has been implicated in various neurological disorders, including schizophrenia, Alzheimer's disease, and epilepsy.

Ovulation is the medical term for the release of a mature egg from an ovary during a woman's menstrual cycle. The released egg travels through the fallopian tube where it may be fertilized by sperm if sexual intercourse has occurred recently. If the egg is not fertilized, it will break down and leave the body along with the uterine lining during menstruation. Ovulation typically occurs around day 14 of a 28-day menstrual cycle, but the timing can vary widely from woman to woman and even from cycle to cycle in the same woman.

During ovulation, there are several physical changes that may occur in a woman's body, such as an increase in basal body temperature, changes in cervical mucus, and mild cramping or discomfort on one side of the lower abdomen (known as mittelschmerz). These symptoms can be used to help predict ovulation and improve the chances of conception.

It's worth noting that some medical conditions, such as polycystic ovary syndrome (PCOS) or premature ovarian failure, may affect ovulation and make it difficult for a woman to become pregnant. In these cases, medical intervention may be necessary to help promote ovulation and increase the chances of conception.

A "knockout" mouse is a genetically engineered mouse in which one or more genes have been deleted or "knocked out" using molecular biology techniques. This allows researchers to study the function of specific genes and their role in various biological processes, as well as potential associations with human diseases. The mice are generated by introducing targeted DNA modifications into embryonic stem cells, which are then used to create a live animal. Knockout mice have been widely used in biomedical research to investigate gene function, disease mechanisms, and potential therapeutic targets.

'Gene expression regulation' refers to the processes that control whether, when, and where a particular gene is expressed, meaning the production of a specific protein or functional RNA encoded by that gene. This complex mechanism can be influenced by various factors such as transcription factors, chromatin remodeling, DNA methylation, non-coding RNAs, and post-transcriptional modifications, among others. Proper regulation of gene expression is crucial for normal cellular function, development, and maintaining homeostasis in living organisms. Dysregulation of gene expression can lead to various diseases, including cancer and genetic disorders.

Growth Differentiation Factor 2 (GDF2), also known as Bone Morphogenetic Protein 9 (BMP9), is a protein that belongs to the transforming growth factor-beta (TGF-β) superfamily. It is a cytokine with important roles in various biological processes, including angiogenesis (the formation of new blood vessels), cardiovascular development, and skeletal muscle regeneration. GDF2/BMP9 is primarily produced by liver cells called hepatocytes and circulates in the bloodstream. It exerts its effects by binding to specific receptors on the cell surface, which triggers intracellular signaling pathways that regulate gene expression and ultimately influence cell behavior.

Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) is a laboratory technique used in molecular biology to amplify and detect specific DNA sequences. This technique is particularly useful for the detection and quantification of RNA viruses, as well as for the analysis of gene expression.

The process involves two main steps: reverse transcription and polymerase chain reaction (PCR). In the first step, reverse transcriptase enzyme is used to convert RNA into complementary DNA (cDNA) by reading the template provided by the RNA molecule. This cDNA then serves as a template for the PCR amplification step.

In the second step, the PCR reaction uses two primers that flank the target DNA sequence and a thermostable polymerase enzyme to repeatedly copy the targeted cDNA sequence. The reaction mixture is heated and cooled in cycles, allowing the primers to anneal to the template, and the polymerase to extend the new strand. This results in exponential amplification of the target DNA sequence, making it possible to detect even small amounts of RNA or cDNA.

RT-PCR is a sensitive and specific technique that has many applications in medical research and diagnostics, including the detection of viruses such as HIV, hepatitis C virus, and SARS-CoV-2 (the virus that causes COVID-19). It can also be used to study gene expression, identify genetic mutations, and diagnose genetic disorders.

C57BL/6 (C57 Black 6) is an inbred strain of laboratory mouse that is widely used in biomedical research. The term "inbred" refers to a strain of animals where matings have been carried out between siblings or other closely related individuals for many generations, resulting in a population that is highly homozygous at most genetic loci.

The C57BL/6 strain was established in 1920 by crossing a female mouse from the dilute brown (DBA) strain with a male mouse from the black strain. The resulting offspring were then interbred for many generations to create the inbred C57BL/6 strain.

C57BL/6 mice are known for their robust health, longevity, and ease of handling, making them a popular choice for researchers. They have been used in a wide range of biomedical research areas, including studies of cancer, immunology, neuroscience, cardiovascular disease, and metabolism.

One of the most notable features of the C57BL/6 strain is its sensitivity to certain genetic modifications, such as the introduction of mutations that lead to obesity or impaired glucose tolerance. This has made it a valuable tool for studying the genetic basis of complex diseases and traits.

Overall, the C57BL/6 inbred mouse strain is an important model organism in biomedical research, providing a valuable resource for understanding the genetic and molecular mechanisms underlying human health and disease.

In situ hybridization (ISH) is a molecular biology technique used to detect and localize specific nucleic acid sequences, such as DNA or RNA, within cells or tissues. This technique involves the use of a labeled probe that is complementary to the target nucleic acid sequence. The probe can be labeled with various types of markers, including radioisotopes, fluorescent dyes, or enzymes.

During the ISH procedure, the labeled probe is hybridized to the target nucleic acid sequence in situ, meaning that the hybridization occurs within the intact cells or tissues. After washing away unbound probe, the location of the labeled probe can be visualized using various methods depending on the type of label used.

In situ hybridization has a wide range of applications in both research and diagnostic settings, including the detection of gene expression patterns, identification of viral infections, and diagnosis of genetic disorders.

Cell proliferation is the process by which cells increase in number, typically through the process of cell division. In the context of biology and medicine, it refers to the reproduction of cells that makes up living tissue, allowing growth, maintenance, and repair. It involves several stages including the transition from a phase of quiescence (G0 phase) to an active phase (G1 phase), DNA replication in the S phase, and mitosis or M phase, where the cell divides into two daughter cells.

Abnormal or uncontrolled cell proliferation is a characteristic feature of many diseases, including cancer, where deregulated cell cycle control leads to excessive and unregulated growth of cells, forming tumors that can invade surrounding tissues and metastasize to distant sites in the body.

Gene expression is the process by which the information encoded in a gene is used to synthesize a functional gene product, such as a protein or RNA molecule. This process involves several steps: transcription, RNA processing, and translation. During transcription, the genetic information in DNA is copied into a complementary RNA molecule, known as messenger RNA (mRNA). The mRNA then undergoes RNA processing, which includes adding a cap and tail to the mRNA and splicing out non-coding regions called introns. The resulting mature mRNA is then translated into a protein on ribosomes in the cytoplasm through the process of translation.

The regulation of gene expression is a complex and highly controlled process that allows cells to respond to changes in their environment, such as growth factors, hormones, and stress signals. This regulation can occur at various stages of gene expression, including transcriptional activation or repression, RNA processing, mRNA stability, and translation. Dysregulation of gene expression has been implicated in many diseases, including cancer, genetic disorders, and neurological conditions.

A base sequence in the context of molecular biology refers to the specific order of nucleotides in a DNA or RNA molecule. In DNA, these nucleotides are adenine (A), guanine (G), cytosine (C), and thymine (T). In RNA, uracil (U) takes the place of thymine. The base sequence contains genetic information that is transcribed into RNA and ultimately translated into proteins. It is the exact order of these bases that determines the genetic code and thus the function of the DNA or RNA molecule.

I apologize, but "sheep" is not a term that has a medical definition. It is a common animal with the scientific name Ovis aries. If you have any medical or health-related questions, I would be happy to try and help answer those for you.

A biological marker, often referred to as a biomarker, is a measurable indicator that reflects the presence or severity of a disease state, or a response to a therapeutic intervention. Biomarkers can be found in various materials such as blood, tissues, or bodily fluids, and they can take many forms, including molecular, histologic, radiographic, or physiological measurements.

In the context of medical research and clinical practice, biomarkers are used for a variety of purposes, such as:

1. Diagnosis: Biomarkers can help diagnose a disease by indicating the presence or absence of a particular condition. For example, prostate-specific antigen (PSA) is a biomarker used to detect prostate cancer.
2. Monitoring: Biomarkers can be used to monitor the progression or regression of a disease over time. For instance, hemoglobin A1c (HbA1c) levels are monitored in diabetes patients to assess long-term blood glucose control.
3. Predicting: Biomarkers can help predict the likelihood of developing a particular disease or the risk of a negative outcome. For example, the presence of certain genetic mutations can indicate an increased risk for breast cancer.
4. Response to treatment: Biomarkers can be used to evaluate the effectiveness of a specific treatment by measuring changes in the biomarker levels before and after the intervention. This is particularly useful in personalized medicine, where treatments are tailored to individual patients based on their unique biomarker profiles.

It's important to note that for a biomarker to be considered clinically valid and useful, it must undergo rigorous validation through well-designed studies, including demonstrating sensitivity, specificity, reproducibility, and clinical relevance.

Recombinant proteins are artificially created proteins produced through the use of recombinant DNA technology. This process involves combining DNA molecules from different sources to create a new set of genes that encode for a specific protein. The resulting recombinant protein can then be expressed, purified, and used for various applications in research, medicine, and industry.

Recombinant proteins are widely used in biomedical research to study protein function, structure, and interactions. They are also used in the development of diagnostic tests, vaccines, and therapeutic drugs. For example, recombinant insulin is a common treatment for diabetes, while recombinant human growth hormone is used to treat growth disorders.

The production of recombinant proteins typically involves the use of host cells, such as bacteria, yeast, or mammalian cells, which are engineered to express the desired protein. The host cells are transformed with a plasmid vector containing the gene of interest, along with regulatory elements that control its expression. Once the host cells are cultured and the protein is expressed, it can be purified using various chromatography techniques.

Overall, recombinant proteins have revolutionized many areas of biology and medicine, enabling researchers to study and manipulate proteins in ways that were previously impossible.

Carrier proteins, also known as transport proteins, are a type of protein that facilitates the movement of molecules across cell membranes. They are responsible for the selective and active transport of ions, sugars, amino acids, and other molecules from one side of the membrane to the other, against their concentration gradient. This process requires energy, usually in the form of ATP (adenosine triphosphate).

Carrier proteins have a specific binding site for the molecule they transport, and undergo conformational changes upon binding, which allows them to move the molecule across the membrane. Once the molecule has been transported, the carrier protein returns to its original conformation, ready to bind and transport another molecule.

Carrier proteins play a crucial role in maintaining the balance of ions and other molecules inside and outside of cells, and are essential for many physiological processes, including nerve impulse transmission, muscle contraction, and nutrient uptake.

Cytokines are a broad and diverse category of small signaling proteins that are secreted by various cells, including immune cells, in response to different stimuli. They play crucial roles in regulating the immune response, inflammation, hematopoiesis, and cellular communication.

Cytokines mediate their effects by binding to specific receptors on the surface of target cells, which triggers intracellular signaling pathways that ultimately result in changes in gene expression, cell behavior, and function. Some key functions of cytokines include:

1. Regulating the activation, differentiation, and proliferation of immune cells such as T cells, B cells, natural killer (NK) cells, and macrophages.
2. Coordinating the inflammatory response by recruiting immune cells to sites of infection or tissue damage and modulating their effector functions.
3. Regulating hematopoiesis, the process of blood cell formation in the bone marrow, by controlling the proliferation, differentiation, and survival of hematopoietic stem and progenitor cells.
4. Modulating the development and function of the nervous system, including neuroinflammation, neuroprotection, and neuroregeneration.

Cytokines can be classified into several categories based on their structure, function, or cellular origin. Some common types of cytokines include interleukins (ILs), interferons (IFNs), tumor necrosis factors (TNFs), chemokines, colony-stimulating factors (CSFs), and transforming growth factors (TGFs). Dysregulation of cytokine production and signaling has been implicated in various pathological conditions, such as autoimmune diseases, chronic inflammation, cancer, and neurodegenerative disorders.

An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.

In the context of physiology and medicine, "kinesis" refers to a type of movement or motion that is spontaneous and not under the direct control of willful thought. It is a broad term that can encompass various forms of involuntary movements in the body, including muscle contractions, heartbeats, and peristalsis (the wave-like muscular contractions that move food through the digestive system).

It's worth noting that "kinesis" is also a term used in the field of psychology to refer to an individual's range of motion or mobility, but this usage is less common in medical contexts.

Bone morphogenetic protein receptors (BMPRs) are a group of transmembrane serine/threonine kinase receptors that play a crucial role in the signaling pathway of bone morphogenetic proteins (BMPs), which are growth factors involved in various biological processes including cell proliferation, differentiation, and apoptosis.

Type I BMPRs include three subtypes: activin receptor-like kinase 2 (ALK2), ALK3 (also known as BMPR-IA), and ALK6 (also known as BMPR-IB). These receptors form a complex with type II BMPRs upon binding of BMP ligands to their extracellular domains. The activation of the receptor complex leads to the phosphorylation of intracellular signaling molecules, such as SMAD proteins, which then translocate to the nucleus and regulate gene expression.

Mutations in type I BMPRs have been associated with several genetic disorders, including hereditary hemorrhagic telangiectasia (HHT), a vascular dysplasia disorder characterized by the formation of abnormal blood vessels. Additionally, alterations in BMP signaling pathways have been implicated in various human diseases, such as cancer, fibrosis, and bone disorders.

"Cattle" is a term used in the agricultural and veterinary fields to refer to domesticated animals of the genus *Bos*, primarily *Bos taurus* (European cattle) and *Bos indicus* (Zebu). These animals are often raised for meat, milk, leather, and labor. They are also known as bovines or cows (for females), bulls (intact males), and steers/bullocks (castrated males). However, in a strict medical definition, "cattle" does not apply to humans or other animals.

Antigens are substances (usually proteins) on the surface of cells, viruses, fungi, or bacteria that can be recognized by the immune system and provoke an immune response. In the context of differentiation, antigens refer to specific markers that identify the developmental stage or lineage of a cell.

Differentiation antigens are proteins or carbohydrates expressed on the surface of cells during various stages of differentiation, which can be used to distinguish between cells at different maturation stages or of different cell types. These antigens play an essential role in the immune system's ability to recognize and respond to abnormal or infected cells while sparing healthy cells.

Examples of differentiation antigens include:

1. CD (cluster of differentiation) molecules: A group of membrane proteins used to identify and define various cell types, such as T cells, B cells, natural killer cells, monocytes, and granulocytes.
2. Lineage-specific antigens: Antigens that are specific to certain cell lineages, such as CD3 for T cells or CD19 for B cells.
3. Maturation markers: Antigens that indicate the maturation stage of a cell, like CD34 and CD38 on hematopoietic stem cells.

Understanding differentiation antigens is crucial in immunology, cancer research, transplantation medicine, and vaccine development.

Cell division is the process by which a single eukaryotic cell (a cell with a true nucleus) divides into two identical daughter cells. This complex process involves several stages, including replication of DNA, separation of chromosomes, and division of the cytoplasm. There are two main types of cell division: mitosis and meiosis.

Mitosis is the type of cell division that results in two genetically identical daughter cells. It is a fundamental process for growth, development, and tissue repair in multicellular organisms. The stages of mitosis include prophase, prometaphase, metaphase, anaphase, and telophase, followed by cytokinesis, which divides the cytoplasm.

Meiosis, on the other hand, is a type of cell division that occurs in the gonads (ovaries and testes) during the production of gametes (sex cells). Meiosis results in four genetically unique daughter cells, each with half the number of chromosomes as the parent cell. This process is essential for sexual reproduction and genetic diversity. The stages of meiosis include meiosis I and meiosis II, which are further divided into prophase, prometaphase, metaphase, anaphase, and telophase.

In summary, cell division is the process by which a single cell divides into two daughter cells, either through mitosis or meiosis. This process is critical for growth, development, tissue repair, and sexual reproduction in multicellular organisms.

Immunohistochemistry (IHC) is a technique used in pathology and laboratory medicine to identify specific proteins or antigens in tissue sections. It combines the principles of immunology and histology to detect the presence and location of these target molecules within cells and tissues. This technique utilizes antibodies that are specific to the protein or antigen of interest, which are then tagged with a detection system such as a chromogen or fluorophore. The stained tissue sections can be examined under a microscope, allowing for the visualization and analysis of the distribution and expression patterns of the target molecule in the context of the tissue architecture. Immunohistochemistry is widely used in diagnostic pathology to help identify various diseases, including cancer, infectious diseases, and immune-mediated disorders.

A cell line is a culture of cells that are grown in a laboratory for use in research. These cells are usually taken from a single cell or group of cells, and they are able to divide and grow continuously in the lab. Cell lines can come from many different sources, including animals, plants, and humans. They are often used in scientific research to study cellular processes, disease mechanisms, and to test new drugs or treatments. Some common types of human cell lines include HeLa cells (which come from a cancer patient named Henrietta Lacks), HEK293 cells (which come from embryonic kidney cells), and HUVEC cells (which come from umbilical vein endothelial cells). It is important to note that cell lines are not the same as primary cells, which are cells that are taken directly from a living organism and have not been grown in the lab.

According to the National Institutes of Health (NIH), stem cells are "initial cells" or "precursor cells" that have the ability to differentiate into many different cell types in the body. They can also divide without limit to replenish other cells for as long as the person or animal is still alive.

There are two main types of stem cells: embryonic stem cells, which come from human embryos, and adult stem cells, which are found in various tissues throughout the body. Embryonic stem cells have the ability to differentiate into all cell types in the body, while adult stem cells have more limited differentiation potential.

Stem cells play an essential role in the development and repair of various tissues and organs in the body. They are currently being studied for their potential use in the treatment of a wide range of diseases and conditions, including cancer, diabetes, heart disease, and neurological disorders. However, more research is needed to fully understand the properties and capabilities of these cells before they can be used safely and effectively in clinical settings.

Transgenic mice are genetically modified rodents that have incorporated foreign DNA (exogenous DNA) into their own genome. This is typically done through the use of recombinant DNA technology, where a specific gene or genetic sequence of interest is isolated and then introduced into the mouse embryo. The resulting transgenic mice can then express the protein encoded by the foreign gene, allowing researchers to study its function in a living organism.

The process of creating transgenic mice usually involves microinjecting the exogenous DNA into the pronucleus of a fertilized egg, which is then implanted into a surrogate mother. The offspring that result from this procedure are screened for the presence of the foreign DNA, and those that carry the desired genetic modification are used to establish a transgenic mouse line.

Transgenic mice have been widely used in biomedical research to model human diseases, study gene function, and test new therapies. They provide a valuable tool for understanding complex biological processes and developing new treatments for a variety of medical conditions.

Transcription factors are proteins that play a crucial role in regulating gene expression by controlling the transcription of DNA to messenger RNA (mRNA). They function by binding to specific DNA sequences, known as response elements, located in the promoter region or enhancer regions of target genes. This binding can either activate or repress the initiation of transcription, depending on the properties and interactions of the particular transcription factor. Transcription factors often act as part of a complex network of regulatory proteins that determine the precise spatiotemporal patterns of gene expression during development, differentiation, and homeostasis in an organism.

Toll-Like Receptor 4 (TLR4) is a type of protein found on the surface of some cells in the human body, including immune cells like macrophages and dendritic cells. It belongs to a class of proteins called pattern recognition receptors (PRRs), which play a crucial role in the innate immune system's response to infection.

TLR4 recognizes and responds to specific molecules found on gram-negative bacteria, such as lipopolysaccharide (LPS), also known as endotoxin. When TLR4 binds to LPS, it triggers a signaling cascade that leads to the activation of immune cells, production of pro-inflammatory cytokines and chemokines, and initiation of the adaptive immune response.

TLR4 is an essential component of the body's defense against gram-negative bacterial infections, but its overactivation can also contribute to the development of various inflammatory diseases, such as sepsis, atherosclerosis, and certain types of cancer.

Paracrine communication is a form of cell-to-cell communication in which a cell releases a signaling molecule, known as a paracrine factor, that acts on nearby cells within the local microenvironment. This type of communication allows for the coordination and regulation of various cellular processes, including growth, differentiation, and survival.

Paracrine factors can be released from a cell through various mechanisms, such as exocytosis or diffusion through the extracellular matrix. Once released, these factors bind to specific receptors on the surface of nearby cells, triggering intracellular signaling pathways that lead to changes in gene expression and cell behavior.

Paracrine communication is an important mechanism for maintaining tissue homeostasis and coordinating responses to injury or disease. For example, during wound healing, paracrine signals released by immune cells can recruit other cells to the site of injury and stimulate their proliferation and differentiation to promote tissue repair.

It's worth noting that paracrine communication should be distinguished from autocrine signaling, where a cell releases a signaling molecule that binds back to its own receptors, and endocrine signaling, where a hormone is released into the bloodstream and travels to distant target cells.

Follicle-Stimulating Hormone (FSH) is a glycoprotein hormone secreted and released by the anterior pituitary gland. In females, it promotes the growth and development of ovarian follicles in the ovary, which ultimately leads to the maturation and release of an egg (ovulation). In males, FSH stimulates the testes to produce sperm. It works in conjunction with luteinizing hormone (LH) to regulate reproductive processes. The secretion of FSH is controlled by the hypothalamic-pituitary-gonadal axis and its release is influenced by the levels of gonadotropin-releasing hormone (GnRH), estrogen, inhibin, and androgens.

The follicular phase is a term used in reproductive endocrinology, which refers to the first part of the menstrual cycle. This phase begins on the first day of menstruation and lasts until ovulation. During this phase, several follicles in the ovaries begin to mature under the influence of follicle-stimulating hormone (FSH) released by the pituitary gland.

Typically, one follicle becomes dominant and continues to mature, while the others regress. The dominant follicle produces increasing amounts of estrogen, which causes the lining of the uterus to thicken in preparation for a possible pregnancy. The follicular phase can vary in length, but on average it lasts about 14 days.

It's important to note that the length and characteristics of the follicular phase can provide valuable information in diagnosing various reproductive disorders, such as polycystic ovary syndrome (PCOS) or thyroid dysfunction.

Activins are a type of protein that belongs to the transforming growth factor-beta (TGF-β) superfamily. They are produced and released by various cells in the body, including those in the ovaries, testes, pituitary gland, and other tissues. Activins play important roles in regulating several biological processes, such as cell growth, differentiation, and apoptosis (programmed cell death).

Activins bind to specific receptors on the surface of cells, leading to the activation of intracellular signaling pathways that control gene expression. They are particularly well-known for their role in reproductive biology, where they help regulate follicle stimulation and hormone production in the ovaries and testes. Activins also have been implicated in various disease processes, including cancer, fibrosis, and inflammation.

There are three main isoforms of activin in humans: activin A, activin B, and inhibin A. While activins and inhibins share similar structures and functions, they have opposite effects on the activity of the pituitary gland. Activins stimulate the production of follicle-stimulating hormone (FSH), while inhibins suppress it. This delicate balance between activins and inhibins helps regulate reproductive function and other physiological processes in the body.

Smad3 protein is a transcription factor that plays a crucial role in the TGF-β (transforming growth factor-beta) signaling pathway. When TGF-β binds to its receptor, it activates Smad3 through phosphorylation. Activated Smad3 then forms a complex with other Smad proteins and translocates into the nucleus where it regulates the transcription of target genes involved in various cellular processes such as proliferation, differentiation, apoptosis, and migration.

Mutations in the SMAD3 gene or dysregulation of the TGF-β/Smad3 signaling pathway have been implicated in several human diseases, including fibrotic disorders, cancer, and Marfan syndrome. Therefore, Smad3 protein is an important target for therapeutic interventions in these conditions.

In the field of medicine, "time factors" refer to the duration of symptoms or time elapsed since the onset of a medical condition, which can have significant implications for diagnosis and treatment. Understanding time factors is crucial in determining the progression of a disease, evaluating the effectiveness of treatments, and making critical decisions regarding patient care.

For example, in stroke management, "time is brain," meaning that rapid intervention within a specific time frame (usually within 4.5 hours) is essential to administering tissue plasminogen activator (tPA), a clot-busting drug that can minimize brain damage and improve patient outcomes. Similarly, in trauma care, the "golden hour" concept emphasizes the importance of providing definitive care within the first 60 minutes after injury to increase survival rates and reduce morbidity.

Time factors also play a role in monitoring the progression of chronic conditions like diabetes or heart disease, where regular follow-ups and assessments help determine appropriate treatment adjustments and prevent complications. In infectious diseases, time factors are crucial for initiating antibiotic therapy and identifying potential outbreaks to control their spread.

Overall, "time factors" encompass the significance of recognizing and acting promptly in various medical scenarios to optimize patient outcomes and provide effective care.

Transforming Growth Factor beta (TGF-β) receptors are a group of cell surface receptors that bind to TGF-β ligands and transduce signals into the cell. These receptors play crucial roles in regulating various cellular processes, including cell growth, differentiation, apoptosis, and extracellular matrix production.

There are two types of TGF-β receptors: type I and type II. Type I receptors, also known as activin receptor-like kinases (ALKs), have serine/threonine kinase activity and include ALK1, ALK2, ALK3, ALK4, ALK5, and ALK6. Type II receptors are constitutively active serine/threonine kinases and include TGF-β RII, ActRII, and ActRIIB.

When a TGF-β ligand binds to a type II receptor, it recruits and phosphorylates a type I receptor, which in turn phosphorylates downstream signaling molecules called Smads. Phosphorylated Smads form complexes with co-Smad proteins and translocate to the nucleus, where they regulate gene expression.

Abnormalities in TGF-β signaling have been implicated in various human diseases, including fibrosis, cancer, and autoimmune disorders. Therefore, understanding the mechanisms of TGF-β receptor function is essential for developing therapeutic strategies to target these conditions.

Gene expression profiling is a laboratory technique used to measure the activity (expression) of thousands of genes at once. This technique allows researchers and clinicians to identify which genes are turned on or off in a particular cell, tissue, or organism under specific conditions, such as during health, disease, development, or in response to various treatments.

The process typically involves isolating RNA from the cells or tissues of interest, converting it into complementary DNA (cDNA), and then using microarray or high-throughput sequencing technologies to determine which genes are expressed and at what levels. The resulting data can be used to identify patterns of gene expression that are associated with specific biological states or processes, providing valuable insights into the underlying molecular mechanisms of diseases and potential targets for therapeutic intervention.

In recent years, gene expression profiling has become an essential tool in various fields, including cancer research, drug discovery, and personalized medicine, where it is used to identify biomarkers of disease, predict patient outcomes, and guide treatment decisions.

Tissue culture techniques refer to the methods used to maintain and grow cells, tissues or organs from multicellular organisms in an artificial environment outside of the living body, called an in vitro culture. These techniques are widely used in various fields such as biology, medicine, and agriculture for research, diagnostics, and therapeutic purposes.

The basic components of tissue culture include a sterile growth medium that contains nutrients, growth factors, and other essential components to support the growth of cells or tissues. The growth medium is often supplemented with antibiotics to prevent contamination by microorganisms. The cells or tissues are cultured in specialized containers called culture vessels, which can be plates, flasks, or dishes, depending on the type and scale of the culture.

There are several types of tissue culture techniques, including:

1. Monolayer Culture: In this technique, cells are grown as a single layer on a flat surface, allowing for easy observation and manipulation of individual cells.
2. Organoid Culture: This method involves growing three-dimensional structures that resemble the organization and function of an organ in vivo.
3. Co-culture: In co-culture, two or more cell types are grown together to study their interactions and communication.
4. Explant Culture: In this technique, small pieces of tissue are cultured to maintain the original structure and organization of the cells within the tissue.
5. Primary Culture: This refers to the initial culture of cells directly isolated from a living organism. These cells can be further subcultured to generate immortalized cell lines.

Tissue culture techniques have numerous applications, such as studying cell behavior, drug development and testing, gene therapy, tissue engineering, and regenerative medicine.

Tretinoin is a form of vitamin A that is used in the treatment of acne vulgaris, fine wrinkles, and dark spots caused by aging or sun damage. It works by increasing the turnover of skin cells, helping to unclog pores and promote the growth of new skin cells. Tretinoin is available as a cream, gel, or liquid, and is usually applied to the affected area once a day in the evening. Common side effects include redness, dryness, and peeling of the skin. It is important to avoid sunlight and use sunscreen while using tretinoin, as it can make the skin more sensitive to the sun.

'Cell lineage' is a term used in biology and medicine to describe the developmental history or relationship of a cell or group of cells to other cells, tracing back to the original progenitor or stem cell. It refers to the series of cell divisions and differentiation events that give rise to specific types of cells in an organism over time.

In simpler terms, cell lineage is like a family tree for cells, showing how they are related to each other through a chain of cell division and specialization events. This concept is important in understanding the development, growth, and maintenance of tissues and organs in living beings.

Toll-like receptors (TLRs) are a type of pattern recognition receptors (PRRs) that play a crucial role in the innate immune system. They are transmembrane proteins located on the surface of various immune cells, including macrophages, dendritic cells, and B cells. TLRs recognize specific patterns of molecules called pathogen-associated molecular patterns (PAMPs) that are found on microbes such as bacteria, viruses, fungi, and parasites.

Once TLRs bind to PAMPs, they initiate a signaling cascade that activates the immune response, leading to the production of cytokines and chemokines, which in turn recruit and activate other immune cells. TLRs also play a role in the adaptive immune response by activating antigen-presenting cells and promoting the differentiation of T cells.

There are ten known human TLRs, each with distinct ligand specificity and cellular localization. TLRs can be found on the cell surface or within endosomes, where they recognize different types of PAMPs. For example, TLR4 recognizes lipopolysaccharides (LPS) found on gram-negative bacteria, while TLR3 recognizes double-stranded RNA from viruses.

Overall, TLRs are critical components of the immune system's ability to detect and respond to infections, and dysregulation of TLR signaling has been implicated in various inflammatory diseases and cancers.

Toll-like receptor 2 (TLR2) is a type of protein belonging to the family of pattern recognition receptors (PRRs), which play a crucial role in the innate immune system's response to pathogens. TLR2 is primarily expressed on the surface of various immune cells, including monocytes, macrophages, dendritic cells, and B cells.

TLR2 recognizes a wide range of microbial components, such as lipopeptides, lipoteichoic acid, and zymosan, derived from both gram-positive and gram-negative bacteria, fungi, and certain viruses. Upon recognition and binding to these ligands, TLR2 initiates a signaling cascade that activates various transcription factors, leading to the production of proinflammatory cytokines, chemokines, and costimulatory molecules. This response is essential for the activation and recruitment of immune cells to the site of infection, thereby contributing to the clearance of invading pathogens.

In summary, TLR2 is a vital pattern recognition receptor that helps the innate immune system detect and respond to various microbial threats by initiating an inflammatory response upon ligand binding.

DNA-binding proteins are a type of protein that have the ability to bind to DNA (deoxyribonucleic acid), the genetic material of organisms. These proteins play crucial roles in various biological processes, such as regulation of gene expression, DNA replication, repair and recombination.

The binding of DNA-binding proteins to specific DNA sequences is mediated by non-covalent interactions, including electrostatic, hydrogen bonding, and van der Waals forces. The specificity of binding is determined by the recognition of particular nucleotide sequences or structural features of the DNA molecule.

DNA-binding proteins can be classified into several categories based on their structure and function, such as transcription factors, histones, and restriction enzymes. Transcription factors are a major class of DNA-binding proteins that regulate gene expression by binding to specific DNA sequences in the promoter region of genes and recruiting other proteins to modulate transcription. Histones are DNA-binding proteins that package DNA into nucleosomes, the basic unit of chromatin structure. Restriction enzymes are DNA-binding proteins that recognize and cleave specific DNA sequences, and are widely used in molecular biology research and biotechnology applications.

"Sex differentiation" is a term used in the field of medicine, specifically in reproductive endocrinology and genetics. It refers to the biological development of sexual characteristics that distinguish males from females. This process is regulated by hormones and genetic factors.

There are two main stages of sex differentiation: genetic sex determination and gonadal sex differentiation. Genetic sex determination occurs at fertilization, where the combination of X and Y chromosomes determines the sex of the individual (typically, XX = female and XY = male). Gonadal sex differentiation then takes place during fetal development, where the genetic sex signals the development of either ovaries or testes.

Once the gonads are formed, they produce hormones that drive further sexual differentiation, leading to the development of internal reproductive structures (such as the uterus and fallopian tubes in females, and the vas deferens and seminal vesicles in males) and external genitalia.

It's important to note that while sex differentiation is typically categorized as male or female, there are individuals who may have variations in their sexual development, leading to intersex conditions. These variations can occur at any stage of the sex differentiation process and can result in a range of physical characteristics that do not fit neatly into male or female categories.

Glycoproteins are complex proteins that contain oligosaccharide chains (glycans) covalently attached to their polypeptide backbone. These glycans are linked to the protein through asparagine residues (N-linked) or serine/threonine residues (O-linked). Glycoproteins play crucial roles in various biological processes, including cell recognition, cell-cell interactions, cell adhesion, and signal transduction. They are widely distributed in nature and can be found on the outer surface of cell membranes, in extracellular fluids, and as components of the extracellular matrix. The structure and composition of glycoproteins can vary significantly depending on their function and location within an organism.

Bone marrow cells are the types of cells found within the bone marrow, which is the spongy tissue inside certain bones in the body. The main function of bone marrow is to produce blood cells. There are two types of bone marrow: red and yellow. Red bone marrow is where most blood cell production takes place, while yellow bone marrow serves as a fat storage site.

The three main types of bone marrow cells are:

1. Hematopoietic stem cells (HSCs): These are immature cells that can differentiate into any type of blood cell, including red blood cells, white blood cells, and platelets. They have the ability to self-renew, meaning they can divide and create more hematopoietic stem cells.
2. Red blood cell progenitors: These are immature cells that will develop into mature red blood cells, also known as erythrocytes. Red blood cells carry oxygen from the lungs to the body's tissues and carbon dioxide back to the lungs.
3. Myeloid and lymphoid white blood cell progenitors: These are immature cells that will develop into various types of white blood cells, which play a crucial role in the body's immune system by fighting infections and diseases. Myeloid progenitors give rise to granulocytes (neutrophils, eosinophils, and basophils), monocytes, and megakaryocytes (which eventually become platelets). Lymphoid progenitors differentiate into B cells, T cells, and natural killer (NK) cells.

Bone marrow cells are essential for maintaining a healthy blood cell count and immune system function. Abnormalities in bone marrow cells can lead to various medical conditions, such as anemia, leukopenia, leukocytosis, thrombocytopenia, or thrombocytosis, depending on the specific type of blood cell affected. Additionally, bone marrow cells are often used in transplantation procedures to treat patients with certain types of cancer, such as leukemia and lymphoma, or other hematologic disorders.

Adaptor proteins are a type of protein that play a crucial role in intracellular signaling pathways by serving as a link between different components of the signaling complex. Specifically, "signal transducing adaptor proteins" refer to those adaptor proteins that are involved in signal transduction processes, where they help to transmit signals from the cell surface receptors to various intracellular effectors. These proteins typically contain modular domains that allow them to interact with multiple partners, thereby facilitating the formation of large signaling complexes and enabling the integration of signals from different pathways.

Signal transducing adaptor proteins can be classified into several families based on their structural features, including the Src homology 2 (SH2) domain, the Src homology 3 (SH3) domain, and the phosphotyrosine-binding (PTB) domain. These domains enable the adaptor proteins to recognize and bind to specific motifs on other signaling molecules, such as receptor tyrosine kinases, G protein-coupled receptors, and cytokine receptors.

One well-known example of a signal transducing adaptor protein is the growth factor receptor-bound protein 2 (Grb2), which contains an SH2 domain that binds to phosphotyrosine residues on activated receptor tyrosine kinases. Grb2 also contains an SH3 domain that interacts with proline-rich motifs on other signaling proteins, such as the guanine nucleotide exchange factor SOS. This interaction facilitates the activation of the Ras small GTPase and downstream signaling pathways involved in cell growth, differentiation, and survival.

Overall, signal transducing adaptor proteins play a critical role in regulating various cellular processes by modulating intracellular signaling pathways in response to extracellular stimuli. Dysregulation of these proteins has been implicated in various diseases, including cancer and inflammatory disorders.

REceptor Activator of NF-kB (RANK) Ligand is a type of protein that plays a crucial role in the immune system and bone metabolism. It belongs to the tumor necrosis factor (TNF) superfamily and is primarily produced by osteoblasts, which are cells responsible for bone formation.

RANK Ligand binds to its receptor RANK, which is found on the surface of osteoclasts, a type of cell involved in bone resorption or breakdown. The binding of RANK Ligand to RANK activates signaling pathways that promote the differentiation, activation, and survival of osteoclasts, thereby increasing bone resorption.

Abnormalities in the RANKL-RANK signaling pathway have been implicated in various bone diseases, such as osteoporosis, rheumatoid arthritis, and certain types of cancer that metastasize to bones. Therefore, targeting this pathway with therapeutic agents has emerged as a promising approach for the treatment of these conditions.

Membrane glycoproteins are proteins that contain oligosaccharide chains (glycans) covalently attached to their polypeptide backbone. They are integral components of biological membranes, spanning the lipid bilayer and playing crucial roles in various cellular processes.

The glycosylation of these proteins occurs in the endoplasmic reticulum (ER) and Golgi apparatus during protein folding and trafficking. The attached glycans can vary in structure, length, and composition, which contributes to the diversity of membrane glycoproteins.

Membrane glycoproteins can be classified into two main types based on their orientation within the lipid bilayer:

1. Type I (N-linked): These glycoproteins have a single transmembrane domain and an extracellular N-terminus, where the oligosaccharides are predominantly attached via asparagine residues (Asn-X-Ser/Thr sequon).
2. Type II (C-linked): These glycoproteins possess two transmembrane domains and an intracellular C-terminus, with the oligosaccharides linked to tryptophan residues via a mannose moiety.

Membrane glycoproteins are involved in various cellular functions, such as:

* Cell adhesion and recognition
* Receptor-mediated signal transduction
* Enzymatic catalysis
* Transport of molecules across membranes
* Cell-cell communication
* Immunological responses

Some examples of membrane glycoproteins include cell surface receptors (e.g., growth factor receptors, cytokine receptors), adhesion molecules (e.g., integrins, cadherins), and transporters (e.g., ion channels, ABC transporters).

Homeodomain proteins are a group of transcription factors that play crucial roles in the development and differentiation of cells in animals and plants. They are characterized by the presence of a highly conserved DNA-binding domain called the homeodomain, which is typically about 60 amino acids long. The homeodomain consists of three helices, with the third helix responsible for recognizing and binding to specific DNA sequences.

Homeodomain proteins are involved in regulating gene expression during embryonic development, tissue maintenance, and organismal growth. They can act as activators or repressors of transcription, depending on the context and the presence of cofactors. Mutations in homeodomain proteins have been associated with various human diseases, including cancer, congenital abnormalities, and neurological disorders.

Some examples of homeodomain proteins include PAX6, which is essential for eye development, HOX genes, which are involved in body patterning, and NANOG, which plays a role in maintaining pluripotency in stem cells.

Immunologic receptors are specialized proteins found on the surface of immune cells that recognize and bind to specific molecules, known as antigens, on the surface of pathogens or infected cells. This binding triggers a series of intracellular signaling events that activate the immune cell and initiate an immune response.

There are several types of immunologic receptors, including:

1. T-cell receptors (TCRs): These receptors are found on the surface of T cells and recognize antigens presented in the context of major histocompatibility complex (MHC) molecules.
2. B-cell receptors (BCRs): These receptors are found on the surface of B cells and recognize free antigens in solution.
3. Pattern recognition receptors (PRRs): These receptors are found inside immune cells and recognize conserved molecular patterns associated with pathogens, such as lipopolysaccharides and flagellin.
4. Fc receptors: These receptors are found on the surface of various immune cells and bind to the constant region of antibodies, mediating effector functions such as phagocytosis and antibody-dependent cellular cytotoxicity (ADCC).

Immunologic receptors play a critical role in the recognition and elimination of pathogens and infected cells, and dysregulation of these receptors can lead to immune disorders and diseases.

Embryonic stem cells are a type of pluripotent stem cell that are derived from the inner cell mass of a blastocyst, which is a very early-stage embryo. These cells have the ability to differentiate into any cell type in the body, making them a promising area of research for regenerative medicine and the study of human development and disease. Embryonic stem cells are typically obtained from surplus embryos created during in vitro fertilization (IVF) procedures, with the consent of the donors. The use of embryonic stem cells is a controversial issue due to ethical concerns surrounding the destruction of human embryos.

Progesterone is a steroid hormone that is primarily produced in the ovaries during the menstrual cycle and in pregnancy. It plays an essential role in preparing the uterus for implantation of a fertilized egg and maintaining the early stages of pregnancy. Progesterone works to thicken the lining of the uterus, creating a nurturing environment for the developing embryo.

During the menstrual cycle, progesterone is produced by the corpus luteum, a temporary structure formed in the ovary after an egg has been released from a follicle during ovulation. If pregnancy does not occur, the levels of progesterone will decrease, leading to the shedding of the uterine lining and menstruation.

In addition to its reproductive functions, progesterone also has various other effects on the body, such as helping to regulate the immune system, supporting bone health, and potentially influencing mood and cognition. Progesterone can be administered medically in the form of oral pills, intramuscular injections, or vaginal suppositories for various purposes, including hormone replacement therapy, contraception, and managing certain gynecological conditions.

Bone Morphogenetic Protein 2 (BMP-2) is a growth factor that belongs to the transforming growth factor-beta (TGF-β) superfamily. It plays a crucial role in bone and cartilage formation, as well as in the regulation of wound healing and embryonic development. BMP-2 stimulates the differentiation of mesenchymal stem cells into osteoblasts, which are cells responsible for bone formation.

BMP-2 has been approved by the US Food and Drug Administration (FDA) as a medical device to promote bone growth in certain spinal fusion surgeries and in the treatment of open fractures that have not healed properly. It is usually administered in the form of a collagen sponge soaked with recombinant human BMP-2 protein, which is a laboratory-produced version of the natural protein.

While BMP-2 has shown promising results in some clinical applications, its use is not without risks and controversies. Some studies have reported adverse effects such as inflammation, ectopic bone formation, and increased rates of cancer, which have raised concerns about its safety and efficacy. Therefore, it is essential to weigh the benefits and risks of BMP-2 therapy on a case-by-case basis and under the guidance of a qualified healthcare professional.

B-lymphocytes, also known as B-cells, are a type of white blood cell that plays a key role in the immune system's response to infection. They are responsible for producing antibodies, which are proteins that help to neutralize or destroy pathogens such as bacteria and viruses.

When a B-lymphocyte encounters a pathogen, it becomes activated and begins to divide and differentiate into plasma cells, which produce and secrete large amounts of antibodies specific to the antigens on the surface of the pathogen. These antibodies bind to the pathogen, marking it for destruction by other immune cells such as neutrophils and macrophages.

B-lymphocytes also have a role in presenting antigens to T-lymphocytes, another type of white blood cell involved in the immune response. This helps to stimulate the activation and proliferation of T-lymphocytes, which can then go on to destroy infected cells or help to coordinate the overall immune response.

Overall, B-lymphocytes are an essential part of the adaptive immune system, providing long-lasting immunity to previously encountered pathogens and helping to protect against future infections.

  • Growth differentiation factor-5 ( GDF5 ) is a gene that tells our body how to make the GDF5 protein (it's common in genetics to give the same name to both a gene and the protein it codes for). (helix.com)
  • Multiple lines of evidence suggest that production of the GDF5 protein in our joints helps our body repair, or replace, damaged cartilage 1-5 . (helix.com)
  • Aside from these environmental factors, studies have shown that some people inherit a specific version of the GDF5 gene which may affect their joint durability 4 . (helix.com)
  • Scientists have found that a change in the GDF5 DNA sequence can reduce how much of the GDF5 protein is made under laboratory conditions 5 . (helix.com)
  • A Functional Polymorphism in the 5′ UTR of GDF5 Is Associated with Susceptibility to Osteoarthritis. (helix.com)
  • Growth and Differentiation Factor 5 (GDF5) is a secreted growth factor that belongs to the Bone Morphogenetic Protein (BMP) family and plays a pivotal role during limb development. (uni-wuerzburg.de)
  • Here, we report on a family with an autosomal dominant inherited combination of Growth and Differentiation Factor 5 (GDF5) is a secreted growth factor that belongs to the Bone Morphogenetic Protein (BMP) family and plays a pivotal role during limb development. (uni-wuerzburg.de)
  • A meta-analysis of European and Asian cohorts reveals a global role of a functional SNP in the 5' UTR of GDF5 with osteoarthritis susceptibility. (cdc.gov)
  • Rs143383 in the growth differentiation factor 5 (GDF5) gene significantly associated with osteoarthritis (OA)-a comprehensive meta-analysis. (cdc.gov)
  • Growth differentiation factor 15 (GDF15) has been associated with food intake and weight regulation in response to metabolic stress. (nature.com)
  • Recently, metabolic research has focused on growth differentiation factor 15 (GDF15), a stress-induced cytokine belonging to the transforming growth factor beta superfamily [ 5 ]. (nature.com)
  • Description: Quantitativecompetitive ELISA kit for measuring Rat growth differentiation factor 15(GDF15) in samples from serum, plasma, tissue homogenates. (scalegen.com)
  • Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Rat Growth Differentiation Factor 15 (GDF15) in serum, plasma, tissue homogenates and other biological fluids. (scalegen.com)
  • We used mass cytometry (CyTOF) and orthotopic cancer mouse models to analyze overall immunological changes after growth differentiation factor 15 (GDF15) gene ablation in HCC. (bmj.com)
  • We recently discovered that Growth Differentiation Factor 15 (GDF15) is a new heart-derived hormone. (upenn.edu)
  • Circulating GDF15 acts on the liver to inhibit growth hormone signaling and body growth. (upenn.edu)
  • GDF15 maturation requires proteolytic cleavage by PCSK3, 5 and 6. (upenn.edu)
  • GDF15 is a heart-derived hormone that regulates body growth. (upenn.edu)
  • The IL-4 gene, IL-3, IL-5, IL-13, and CSF2 form a cytokine gene cluster on chromosome 5q. (fishersci.com)
  • The protein encoded by this gene is a cytokine that acts as a growth and differentiation factor for both B cells and eosinophils. (antibodies-online.com)
  • The receptor of this cytokine is a heterodimer, whose beta subunit is shared with the receptors for interleukine 3 (IL3) and colony stimulating factor 2 (CSF2/GM-CSF). (antibodies-online.com)
  • This gene, together with those for interleukin 4 (IL4), interleukin 13 (IL13), and CSF2, form a cytokine gene cluster on chromosome 5. (antibodies-online.com)
  • Remarkably, Clec4a4+ eosinophils were instructed by the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor that imprints many gut immune cells. (stanford.edu)
  • IL-5 has been shown to promote the growth of immature hematopoietic BFU-E progenitors, stimulate the activation and differentiation of eosinophils, and promote the generation of cytotoxic lymphocytes. (biolegend.com)
  • IL-5 is a potent T-cell derived factor that stimulates the growth of certain B cells and the differentiation of eosinophils. (biovision.com)
  • PLOS Genetics 2017 May 8;13(5):e1006750. (stanford.edu)
  • 2017 ). It appears from their investigations that genetic factors seem to exert a significant influence on the carcinogenesis of the cervix. (researchsquare.com)
  • Odontoblast marker gene levels, on the other hand, were significantly elevated after seven days of culture in the presence of GDF-5. (ispub.com)
  • GDF-5 also increased the gene expression and enzyme activity of alkaline phosphatase. (ispub.com)
  • Along with other BMPs, including BMP-2, -4 and -7, which are well known as potent osteoinductive growth factors, GDF-5 plays important roles in the development of bones, cartilage and tendons, as evidenced by the tendency for the gene and protein expression levels of GDF-5 to increase over time in these tissues. (ispub.com)
  • 2002). It has also been reported that the GDF-5 gene is expressed in dental sac, periodontal ligament, dental pulp cells, and odontoblasts during tooth development (Morotome et al. (ispub.com)
  • -592C/A polymorphism of IL-10 gene may be considered a risk factor for cervical cancer. (researchsquare.com)
  • SNP − 592C/A of the IL-10 gene promoter is located near a number of transcription factor binding sites. (researchsquare.com)
  • This study evaluates the effect of A. montana leaves hexane extract on several signaling cascades and gene expression in metastatic breast cancer cells upon insulin-like growth factor-1 (IGF-1) stimulation. (techscience.com)
  • Correlation between growth differentiation factor 5 (rs143383) gene polymorphism and knee osteoarthritis: an updated systematic review and meta-analysis. (cdc.gov)
  • In addition we will address important areas of modern epidemiology such as the influence of early life factors on adult health and disease, but also the importance of the gene-diet-microbiota interaction for body function and health. (lu.se)
  • Med Princ Pract (2023) 32 (4-5): 297-307. (karger.com)
  • In this study, we assayed the effect of exogenous mouse recombinant GDF-5 on cell proliferation of dental pulp cells and determined the expression levels of odontoblast differentiation marker genes in the cells of isolated mouse dental pulp tissues in the presence of GDF-5. (ispub.com)
  • This product is manufactured by BioVision, an Abcam company and was previously called 4580 BMP-14 (GDF-5/CDMP-1), human recombinant. (abcam.com)
  • An odontogenic medium modified by the addition of recombinant human bone morphogenetic protein 2 was used in the experimental groups to induce differentiation. (scielo.br)
  • Yet it remains poorly understood how these factors can induce the various types of cells in the dental pulp to engage in a harmonized and coordinated process of dentin regeneration. (ispub.com)
  • These findings are expected to improve our knowledge of the role of GDF-5 in dental tissue development and to provide information that may be useful in the application of GDF-5 as a molecular manipulator in dental tissue regeneration. (ispub.com)
  • Nerve growth factor combined with vascular endothelial growth factor enhances regeneration of bladder acellular matrix graft in spinal cord injury-induced neurogenic rat bladder. (ucsf.edu)
  • Effect of vascular endothelial growth factor on regeneration of bladder acellular matrix graft: histologic and functional evaluation. (ucsf.edu)
  • The application of specific growth factors for osteoinduction without using a bone graft constitutes a real impact on bone regeneration. (allenpress.com)
  • A variety of growth factors (GFs)-including bone morphogenetic protein (BMP), platelet-derived growth factor (PDGF), and peptides of the parathyroid hormone (PTH)-have been tested for local bone regeneration. (allenpress.com)
  • They are responsible for several biological activities involving tissue morphogenesis, regeneration, healing, and cell differentiation processes. (allenpress.com)
  • Consequently, PLDL and PDL seemed to be promising scaffold candidates for odontogenic regeneration at least as HA-TCP, when they were applied with the DPSC induced for odontogenic differentiation. (scielo.br)
  • now reveal that differentiation of USCs generates ECs with robust endothelial function in vitro and endothelial potential in vivo, thereby suggesting this approach as a non-invasive, simple, and low-cost method [5] to produce sufficient autologous ECs for applications in tissue-engineered vascular regeneration or the repair of endothelial dysfunction [6]. (stemcellsportal.com)
  • The cartilage-specific localization pattern of these novel TGF-β superfamily members, which contrasts with the more ubiquitous presence of other BMP family members, suggests a potential role for these proteins in chondrocyte differentiation and growth of long bones. (elsevierpure.com)
  • This inhibits chondrocyte differentiation, and growth plate function is severely compromised. (medscape.com)
  • This IL-5 protein is useful as a standard for a human IL-5 sandwich ELISA, using unlabeled JES1-39D10 antibody (catalog #500902) for capture and biotinylated JES1-5A10 antibody (catalog #501002) for detection. (biolegend.com)
  • Control of muscle differentiation in BC3H1 cells by fibroblast growth factor and vanadate. (wustl.edu)
  • The disorder is caused by a dominantly inherited FGFR3 mutation that permanently activates the fibroblast growth factor receptor 3 (FGFR3) and its downstream mitogen-activated protein kinase (MAPK) signaling pathway. (medscape.com)
  • Kim and Morshead, 2003), and the fibroblast that SSEA4 associated with CD133 can be used for growth factor (FGF) receptor 4 (Cai et al. (lu.se)
  • Functional Analysis Of The Growth And Differentiation Factor 5 Regulatory Polymorphism That Is Associated With Osteoarthritis Susceptibility. (helix.com)
  • Association between growth differentiation factor 5 rs143383 genetic polymorphism and the risk of knee osteoarthritis among Caucasian but not Asian: a meta-analysis. (cdc.gov)
  • There were no significant differences in dental pulp cell proliferation patterns related to the absence or presence of GDF-5 after seven days of culture. (ispub.com)
  • These results indicate that, although GDF-5 may have no effect on cell proliferation in isolated dental pulp tissue, it could promote odontoblast differentiation. (ispub.com)
  • 2003). A previous in-vitro study on the role of GDF-5 in periodontal ligament cells has shown that exogenous GDF-5 promotes cell proliferation while suppressing the activity of alkaline phosphatase (ALP), which is closely related to tissue calcification and which is secreted during the formation of tissue calcifications. (ispub.com)
  • Here, we investigated the effect of GDF-5 on the proliferation of dental pulp cells and their differentiation into odontoblasts by assaying the expression levels of odontoblast marker genes. (ispub.com)
  • Complex subunit associated factors are involved in hybridoma growth, Eosinohils, eritroid proliferation and derived from promotor binding stimulating subunits on the DNA binding complex. (tgf-a.com)
  • In addition, overexpression of ZYX in hepatoma cell lines (PLC/PRF/5, HCCLM3) enhanced their proliferation, migration and invasion, whereas ZYX knockdown had the opposite effects (SK HEP-1, Huh-7). (techscience.com)
  • Although the exact molecular mechanism of the RA pathogenesis remains elusive, proinflammatory cytokines including tumor necrosis factor- (TNF-) α and interleukin- (IL-) 1 β and autoreactive T cells are known to play central roles in the development and progression of RA [ 1 ]. (hindawi.com)
  • Furthermore, the expression of apoptosis factors (caspase-3 and caspase-8), inflammatory factors [interleukin (IL)-1, IL-6] and matrix degradation enzymes [matrix metalloproteinase (MMP)-3, MMP-13] were also significantly increased. (edu.au)
  • Abstract Fos-related antigen 1 (Fra-1) is a nuclear transcription factor that regulates cell growth, differentiation, and apoptosis. (techscience.com)
  • Abstract Pancreatic cancer is one of the most aggressive cancers with a median survival time of less than 5 months, and conventional chemotherapeutics are the main treatment strategy. (techscience.com)
  • ABSTRACT We evaluated the prognostic value of serum endostatin and vascular endothelial growth factor (VEGF) for diagnosis of pre-eclampsia. (who.int)
  • To date, various studies have reported that cells isolated from the dental pulp of various animals can be induced to differentiate into cells of the odontoblastic phenotype by means of various chemicals, growth factors and signaling molecules both in vitro and in vivo ( reviewed in Nakashima and Akamine, 2005). (ispub.com)
  • The odontogenic differentiation of human dental pulp stem cells on nanofibrous poly(L-lactic acid) scaffolds in vitro and in vivo. (scielo.br)
  • This IL-5 protein is biologically active, and can be used for in vitro assays. (biolegend.com)
  • Cells derived from bone marrow can undergo osteoinduction in vitro in the absence of osteoinductive factors such as bone morphogenetic proteins. (bvsalud.org)
  • To date, various studies have reported that BMP-family growth factors can induce cells isolated from dental pulp tissues to differentiate into odontoblasts. (ispub.com)
  • The EC 50 as determined by its ability to induce alkaline phosphatase production by ATDC-5 chondrogenic cells is 1-10 µg/ml. (abcam.com)
  • Description: A sandwich ELISA kit for detection of Growth Differentiation Factor 1 from Rat in samples from blood, serum, plasma, cell culture fluid and other biological fluids. (thescientistconnect.com)
  • 5 , 6 In concordance with the role of nodal cilia in L-R asymmetry, mutations in the motor proteins Kif3A and Kif3B, and the transcription factor Foxj1 in the mouse have demonstrated that ciliary motility is important for L-R asymmetry. (bmj.com)
  • We associated lineage-determining transcription factors (LDTFs) with demethylation and demonstrated unique patterns of DNA methylation/hydroxymethylation in relationship to open chromatin regions (OCRs), histone modifications and TF-binding sites. (stanford.edu)
  • Aplha, transcription related growth factors and stimulating factors or repressing nuclear factors are complex subunits of proteins involved in cell differentiation. (tgf-a.com)
  • Ident- cult to deduce interaction rules from observations of the ified transcription factors for specific cell fates are, for entire system. (lu.se)
  • Growth/differentiation factor-5 (GDF-5) belongs to the bone morphogenetic protein (BMP) family, which is expressed in dental pulp tissues. (ispub.com)
  • Nevertheless, the effect of GDF-5 on odontoblast differentiation from dental pulp tissues remains unknown. (ispub.com)
  • Furthermore, dental pulp cells cultured in the presence of GDF-5 formed alizarin red-positive nodules after 10 days of culture. (ispub.com)
  • In dental pulp cells, however, the functions of GDF-5 are still unknown. (ispub.com)
  • This study was designed to determine the in vivo performance of three different materials as scaffolds for dental pulp stem cells (DPSC) undergoing induced odontogenic differentiation. (scielo.br)
  • Growth/differentiation factor-5 (GDF-5) is a member of the bone morphogenetic protein (BMP) family, which is a subgroup of the transforming growth factor- (TGF-) superfamily. (ispub.com)
  • By the late 1980s, the active factor responsible for the induction of bone was identified: BMP. (allenpress.com)
  • IL-17 not only induces proinflammatory cytokines, but also directly enhances osteoclastogenesis by upregulating receptor activator nuclear kappa ligand (RANKL) on osteoblasts [ 5 ], contributing to bone erosion in RA. (hindawi.com)
  • Bone morphogenetic proteins (BMP), known as active components of odontogenic differentiation and tooth development, have been used as a growth factor in an appropriate medium. (scielo.br)
  • Osteoblasts were obtained from human bone marrow cells even in the absence of growth factors and showed a typical morphology. (bvsalud.org)
  • Conclusions: This study showed that an osteoblastic cell lineage may be obtained from human bone marrow derived from adherent cells, and that the presence of the rhBMP-4 seems to have an effect during the first stages of differentiation only. (bvsalud.org)
  • and double heterozygosity in bone growth disorders. (medscape.com)
  • Therefore, the long bones are short but wide because appositional bone growth is unaffected. (medscape.com)
  • This markedly diminished growth results not only from abnormal endochondral bone growth but also from abnormal placement and premature fusion of the synchondroses. (medscape.com)
  • Human Urine-Derived Stem Cell Differentiation to Endothelial Cells with Barrier Function and Nitric Oxide Production. (stemcellsportal.com)
  • Here, we characterized the whole-genome distribution of methyl-CpG and 5-hydroxymethylcytosine (5hmC) in mouse innate lymphoid cell 3 (ILC3), ILC2 and natural killer (NK) cells. (stanford.edu)
  • they are capable of stimulating the differentiation of pluripotent mesenchymal cells to osteoprogenitor cells. (allenpress.com)
  • See More Use our definitive endoderm (DE) differentiation kit to obtain functional DE cells that are capable of downstream differentiation to hepatic, intestinal, pancreatic and pulmonary cells. (stemcell.com)
  • The inhibitory effect of RGE on Th17 differentiation and osteoclastogenesis observed in mice was also confirmed in the subsequent experiments performed using human peripheral blood mononuclear cells. (hindawi.com)
  • Transforming growth factor- (TGF-) β and IL-6 primes initial differentiation and IL-23 promotes functional maturation of Th17 cells [ 7 ]. (hindawi.com)
  • Intelligent Information gives birth to Life: it is the factors existing at 5 stages of stem cells differentiation that determine the fate of healthy and pathological cells. (biava.me)
  • Fortunately, today, thanks to the stem cells growth and differentiation factors taken at specific stages of embryonic life, it is possible to stop cellular senescence and thus prevent neurodegeneration. (biava.me)
  • Indeed, whenever all the substances present at all different differentiation stages were obtained, we would have had the entire epigenetic code available, that is the code that can regulate all the genes of all the cells that make up an entire organism. (biava.me)
  • In that moment starting from a single totipotent stem cell (the fertilized egg) a differentiation of all types of stem cells through different stages occurs: pluripotent, multipotent, oligopotent stem cells, cells in progress of definitive differentiation and finally fully differentiated cells. (biava.me)
  • It has been shown that the completeness of information and the redundancy of epigenetic code factors can significantly impede the degeneration of nerve cells (this is because initially the redundancy of factors, i.e. factors present from the beginning to the end of the differentiation process, first expands the number of stem cells and then differentiates them into specific tissues). (biava.me)
  • Methods We used matched tumor tissues and blood samples from 150 patients with HCC to identify key factors of Treg cells expansion. (bmj.com)
  • They have a higher odontogenic differentiation capacity compared to other cell groups due to their content of specific progenitor cells. (scielo.br)
  • IL-5 is a homodimeric, disulphide-linked protein produced by T-cells. (biolegend.com)
  • As a means to generate sufficient autologous ECs, researchers from the laboratory of Yuanyuan Zhang (Wake Forest School of Medicine, Winston-Salem, NC, USA) recently assessed the possible differentiation of ECs from urine-derived stem cells (USCs), cells originating from the parietal cells in kidney glomeruli that possess robust proliferative abilities, multipotent differentiation capacity, and robust paracrine-acting effects [1-4]. (stemcellsportal.com)
  • Differentiation of USCs in endothelial medium generated EC-like cells by day 14 that displayed endothelial characteristics at the morphological, ultrastructural (tight junction formation), and functional marker expression levels (e.g. (stemcellsportal.com)
  • Multipotential differentiation of human urine-derived stem cells: potential for therapeutic applications in urology. (stemcellsportal.com)
  • Skeletal myogenic differentiation of urine-derived stem cells and angiogenesis using microbeads loaded with growth factors. (stemcellsportal.com)
  • that regulate the differentiation and activation of these cells. (cdc.gov)
  • As human osteosarcoma cells are a source of additional growth they did not affect osteoinduction. (bvsalud.org)
  • Similarly, expression levels of the translation factors were investigated in human prostate epithelial cells, RWPE1, exposed to a cytotoxic concentration of cadmium chloride. (cdc.gov)
  • Translation initiation factor 5A2 (TIF5A2) and translation elongation factor 1delta (TEF1 delta) also exhibited significant overexpression (10- and 5-fold overexpression, respectively) in the tumor cells compared with the corresponding control cells. (cdc.gov)
  • Exposure of RWPE1 cells to a cytotoxic concentration of cadmium chloride also resulted in overexpression of several translation factors. (cdc.gov)
  • The cells were thawed and resus- disease control measures in ACL [5]. (who.int)
  • Growth differentiation factors (GDFs) are a subfamily of proteins belonging to the transforming growth factor beta superfamily that have functions predominantly in development. (wikipedia.org)
  • Their carboxyl-terminal TGF-β domains are 82% identical, thus defining a novel subfamily most closely related to BMP-5, BMP-6, and osteogenic protein-1. (elsevierpure.com)
  • And that is what has been done, starting from choosing a specific embryo as a model for cell differentiation study: in this case it was chosen an embryo of Zebrafish. (biava.me)
  • Whether some of these proteins are causally involved in the pathogenesis of clustering of multiple risk factors in the same individual remains to be investigated. (lu.se)
  • cell differentiation. (ispub.com)
  • PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. (antikoerper-online.de)
  • Stem Cell Res Ther 2014;5:69. (stemcellsportal.com)
  • Here, we reported that mammalian target of rapamycin complex 2 (mTORC2) kinase is overexpressed in pancreatic cancer tissues and promotes pancreatic cancer cell growth and invasion. (techscience.com)
  • Translation factors control the translation of all proteins including those vital for cell growth and differentiation as well as those involved in cellular response to chemical toxicity. (cdc.gov)
  • By employing the real time PCR technique, we have investigated the expression levels of various translation factors in human cancer cell lines and their corresponding controls. (cdc.gov)
  • Among the translation factors studied, the expression level of translation elongation factor 1A2 (TEF1A2) exhibited the highest alteration (approximately 2000-fold overexpression) in the cancer cell lines compared with the corresponding controls. (cdc.gov)
  • Recent advances in live imaging and genetics of mammalian division, movement and cell differentiation leading to development which integrate observations of biochemical tissue formation [14 ]. (lu.se)
  • Other synovial fluid findings that aid in the differentiation of osteoarthritis from other conditions are negative Gram stains and cultures, as well as the absence of crystals when fluid is viewed under a polarized microscope. (medscape.com)
  • Transforming Growth Factor-beta ( TGF-beta , TGF-β) this is a superfamily signaling pathway with many different roles during development. (edu.au)
  • Two novel members of the transforming growth factor-β (TGF-β) superfamily were identified and designated cartilage-derived morphogenetic protein-1 (CDMP-1) and -2 (CDMP-2). (elsevierpure.com)
  • In addition, development and genetic studies have shown that GDF-5 null mutation or transgenic mice exhibit abnormal growth patterns or overgrowth of limbs, long bones, cartilage, joints and digits (Storm et al. (ispub.com)
  • The study provides basic information on the development of the early embryo, which could lead to insights on the genetic factors underlying newborn heart malformations and other birth defects involving the left-right positioning of the internal organs. (nih.gov)
  • This condition results from a combination of genetic, environmental, and lifestyle factors, some of which have not been identified. (medlineplus.gov)
  • Variations in the genes that provide instructions for making opioid receptors have been studied extensively as genetic risk factors for opioid addiction. (medlineplus.gov)
  • Find IL-5 Antibodies for a variety of species such as anti-Human IL-5, anti-Mouse IL-5, anti-Rat IL-5. (antibodies-online.com)
  • Monomeric human IL-5 is a 126 amino acid protein with a reported molecular weight of 26 kD for the homodimeric protein. (biolegend.com)
  • Mouse and human IL-5 are approximately 70% identical. (biolegend.com)
  • Human IL-5 is a 26.5 kDa protein containing 232 amino acid residues. (biovision.com)
  • In the 14 mm embryo, the foot will continue to develop so that the 5 rays evolve into a more fanlike structure. (medscape.com)
  • The possibility of studying the entire epigenetic code exists only in the embryo and only in the period when differentiation of all organs and apparatus occurs. (biava.me)
  • Immunohistochemistry results showed decreased expression of transforming growth factor beta (TGFβ) signaling pathway. (edu.au)
  • ENG and ALK1 code for proteins involved in the transforming growth factor (TGF)-β1 signaling pathway, and it is widely accepted that HHT pathogenicity results from haploinsufficiency. (aspetjournals.org)
  • Thus only at the time when it was decided to study the epigenetic regulation code, i.e. the period of differentiation of various organs and apparatus, it became possible to study all the different and incredible regulatory abilities of that code. (biava.me)
  • Description: A sandwich quantitative ELISA assay kit for detection of Rat Growth Differentiation Factor 1 (GDF1) in samples from serum, plasma or other biological fluids. (thescientistconnect.com)
  • Twenty-two proteins were significantly related to all 5 MetS components, and of those, 20 were with MetS as a binary outcome (n = 600, 24% of the sample) following adjustment for age, sex, fat mass, and lifestyle factors (alcohol intake, smoking, education, and exercise habits). (lu.se)
  • Therefore, RGE can ameliorate arthritis in mice with CIA by targeting pathogenic Th17 and osteoclast differentiation, suggesting a novel therapy for treatment of RA. (hindawi.com)
  • This review summarizes evidence for the role of proteolytic enzymes that degrade and inactivate insulin-like growth factor binding proteins (IGFBP) during follicular development in mammals. (bioone.org)
  • Vascular growth during implantation normal non-pregnant controls, 20 normal and placentation is critical for successful pregnant controls, 20 patients with mild gestation. (who.int)
  • Alterations in the expression of translation factors as molecular markers of carcinogenesis and chemical toxicity. (cdc.gov)
  • Further studies have been performed in our laboratory to determine whether alterations in the expression of various translation (initiation, elongation, and termination) factors can be used as molecular markers for carcinogenesis and chemical toxicity. (cdc.gov)
  • These results thus demonstrate that translation factors may be cellular targets for carcinogenesis and chemical toxicity, and that alterations in their expression levels may be used as molecular marker for carcinogenesis and chemical toxicity. (cdc.gov)

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